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THE SINGER’S VOICE
Cantor Stephen Chaiet
NATS National Assoc. Teachers of Singing
The National website for NATS dedicated to encouraging the highest standards of singing through excellence in teaching and the promotion of vocal education and research. http://www.nats.org/
Vocal Instructors with the NATS represent those voice teachers exhibiting the highest levels of training and expertise. The website link below will direct you to those teachers affiliated with the Toronto Ontario Great Lakes Chapter. The Toronto contingent of NATS voice teachers represents one of the largest bodies of highly trained professionals assembled from both Canada,USA & worldwide. http://www.natsontario.org/
A VERY IMPORTANT UPDATE CONCERNING CANTOR CHAIET’S RETINITIS PIGMENTOSA CONDITION – RP59 PLEASE SCROLL DOWN TO THE RP 59 UPDATE SECTION FOR IMPORTANT INFORMATION FOR RELATIVES AND FRIENDS
VOICE REHABILITATION FOR THE MODERN,
CLASSICAL, OPERATIC & LITURGICAL SINGER
The Human Voice
The Human Voice is both socially, physically and even spiritually, one of our most special attributes. Your voice cannot be touched, tasted, smelled or seen. Yet throughout human history, it has been responsible for influencing the course of music, art, religion and politics. Whether spoken or sung aloud the result of hearing the voice in speech or song has inspired men and women to greatness in every human field of endeavor. Your own unique expression of vocal sound through vocal acculturation and rehabilitation is one of the goals of this website.
There are those of us who have always wanted to learn how to sing. Regardless of your singing style the first rule of thumb is : ‘prima non nocere ‘ – firstly to do no harm. This website and its links will always promote this rule both through instruction and emphasis on vocal hygiene. During his active career this has always been Cantor Stephen Chaiet’s vocal philosophy both in performance and studio instruction. Any questions relating to these aspects of the vocal art may be conveyed via the guest page of this website . Responses will be for the purpose of dispensing valuable information concerning the Bel Canto teaching methods, holistic therapies, and the nutritional preservation of the vocal instrument. Website links are provided toward this end on this site and will be modified as the need arises. Best wishes for success in your search for vocal health, fitness and fulfillment!
Recommended Sites
Peterson Voice Studio -Justin Petersen
https://petersenvoicestudio.com/
Singing for a Living Marta Woodhull
Home
The VoiceTeacher with Maestro David Jones
THE VOICE DOCTOR (pre/post operative orientation site)
http://www.voicedoctor.net
NATS Professor Richard Miller in memoriam (especially for our NATS Students)
https://www.oberlin.edu/conservatory/divisions/vocal-studies/richard-miller-classical-voice-competition/about-richard-miller
https://www.singers.com/vocal-coach/Richard-Miller/
NATS Official Website National Association of Teachers of Singing of America NATS America
http://www.nats.org/
Lisa Popeil Voiceworks
http://www.popeil.com
Antonio (Anthony) Frisella in memorium
Cantor Stephen Chaiet – Singer & Voice Teacher
VOICE REHABILITATION
‘…his flexibility and range are positively astonishing’ Jacob Siskind – The Ottawa Citizen
‘…the art of Cantorial singing is alive and well’ Jacob Siskind – The Canadian Jewish News
Cantor Stephen Chaiet is an acclaimed lyric tenor, liturgical singer, cantor, and operatic – classical singer for over twenty years. Although presently , no longer a practicing Cantor, his performances at the Canadian Museum of Civilization, the National Gallery Concert Hall of Canada, the National Arts Centre, Nepean’s Centrepointe Theatre, on CBC Arts Radio hosted by Shelly Solmes and on CJOH television’s Regional Contact were enthusiastically received and were firsts for a Cantor in Ottawa, Canada. As an acclaimed Concert singer, Recitalist, Voice teacher and Adjudicator for the National Association of Teachers of Singing NATS for many years in Ottawa Ontario CANADA and in Toronto Ontario CANADA, his specialty is in voice restoration, vocal rehabilitation, classical and modern singing instruction and liturgical/ cantorial coaching. He has been a much sought-after speaker and writer on these subjects, while having maintained an active career as a Cantor (precentor) . His voice students (whether seeking rehab or vocal training) have been performers from a variety of musical genres – cantors and cantorial soloists (with CDs produced), popular blues singers (Maples Blues Award Winners performing on stages worldwide), operatic and concert-oratorio performers, popular swing and hip-hop artists, jazz and reggae musicians as well as many ethnic-language singers.
In consultation with prominent otolaryngologists he has had great success in preserving the voices of both popular classical and modern singers. (previous link above from The Voice Doctor) Singers possessing vocal tremelos (wobble), poor pitch-intonation or singers displaying nasality, unconventional tonal concepts, dysphonia, stuttering, or pre- and post- operative surgical nodules have sought him for voice therapy. He also has specialized in restorative nutrition for singers, dancers and actors utilizing the latest herbal, holistic and homeopathic protocols. In addition to successfully auditioning for the Canadian Opera Company and the Opera Company of Hamilton, he also had a distinguished career firstly as an Associate Cantor in Toronto, Canada (1983-1989), and as later as a Senior Cantor in Ottawa (1989-2003) in the National Capital of Canada. Cantor Chaiet has worked with some of the finest choirs in Canada, concertizing with the Canadian Centennial Choir https://ccc-ccc.ca/history-of-the-choir/ under the baton of James Caswell, with the Statistics Canada Choir and with other numerous choral ensembles . He was a contributor and musical proof-reader for Clifford Ford’s now famous volume ” Sacred Choral Music III (of the Canadian Musical Heritage series) and is mentioned in Ford’s acknowledgments. He has performed with combined choirs at the National Arts Centre for two performances with conductor Franz Paul Decker to wonderful reviews in the national media (CBC radio and the Ottawa Citizen).
He was accepted as an honoured member and alumnus of the NATS National Association of Teachers of Singing (Montreal Chapitre Quebec, Ottawa Chapter, Toronto Ontario Great Lakes Chapter), the National Music Council of America, and the CCA Cantorial Council of America . He received his Cantorial Ordination and Diploma, approved by the Toronto Cantorial Council, from the late world famous Cantor David Bagley after lengthy study, and a Cantorial designate diploma from the Cantorial Council of America CCA Belz Institute New York. After being influenced by the Bel Canto style of the late Cantor Louis Danto in his choir as a youth, he later continued his classical training at the Royal Conservatory of Music in Toronto with Madames Irene MacLellan and Fanny Levitan along with vocal coach and accompanist Bram Goldhamer. He also holds certificates from the National Association of Teachers of Singing of America NATS in Vocal Pedagogy and Rehabilitation using the techniques of the late Professors Richard Miller and Antonio Frisella of the Metropolitan Opera Co.
He has also acted as an Adjudicator for the NATS annual vocal competitions held annually throughout Canada and the United States. In the area of Technical Designation and Direction for the acclaimed production of Shakespeare’s ‘Merchant of Venice in Auschwitz’ , he acted as the musical/cultural consultant for the production which has been performed worldwide.
Cantor Stephen Chaiet has been a contributor of articles for the Cantorial Council of America’s – 40th Year Commemorative Book, writing extensively on Voice Rehabilitation, Hygiene & Nutritional Protocols for Vocalists. As previously mentioned, he has also been musical advisor to the Canadian Musical Heritage Society as a contributor, especially in the production of the Sacred Choral Music Volume III available to doctoral students of music globally. He is featured and interviewed in the book From Chantre to Djak: Cantorial Traditions in Canada authored by Robert B. Klymasz , Curator at the Canadian Museum of Civilization. https://www.amazon.ca/chantre-djak-Cantorial-traditions-Canada/dp/0660178346
A VERY IMPORTANT UPDATE CONCERNING CANTOR CHAIET’S RETINITIS PIGMENTOSA CONDITION – RP59
A recent genetic discovery of Cantor Chaiet’s Retinitis Pigmentosa genotype was made as of November 2022 – RP 59 done under the purview of Dr. Nupura Bakshi (Retinal Specialist) and Dr. Chantal Morel (Metabolic Geneticist). Buccal-cheek swab samples were sent to Advanced Genetic labs in Finland where the RP 59 gene was finally discovered. RP 59 is is homozygous for DHDDS c.124A>G, p.(Lys42Glu), which is pathogenic for visual loss – DHDDS c.124A>G, p.(Lys42Glu) is classified as pathogenic, based on currently available evidence supporting its disease-causing role. Retinitis pigmentosa 59 caused by DHDDS variants is inherited in an autosomal recessive manner. The patient is homozygous for the variant, which is consistent with autosomal recessive inheritance. Homozygous means that both patient’s parents (mother and father) are each confirmed to be carriers of this variant – any siblings of the patient will have a 25%chanceof being homozygous for the variant and have
a 50% chance of being an asymptomatic carrier. If you are a relative of Cantor Chaiet’s on either his mother’s or father’s side it is advised that you can also be genetically tested in order to determine if you carry the RP 59 gene. This will help to further research towards a treatment for this retinal dystrophy/disorder. In 2024-2026 the ongoing research is promising. You may contact Dr. Chantal F.J. Morel at the Fred A. Litwin Family Centre in Genetic Medicine (University Health Network & Mt. Sinai Hospital) at 416-586-4800 extension 4220 and/or fax 416-619-5523. For relatives there is no fee for this service and Dr. Chantal Morel has advised Cantor Chaiet to encourage family members to contact her office especially through this website.
Cantor Stephen Chaiet’s Retinal Physicians :
Dr. Keyvan Koushan https://www.torontoretinainstitute.com/dr-koushan.html#/
Dr. Nupura Bakshi https://www.youtube.com/watch?v=ZqjFwOYrs1w
Dr. Stephen Dorrepaal https://clarityeye.ca/doctors/stephen-dorrepaal/
https://www.uhn.ca/Medicine/Clinics/Genetic_Medicine_Clinic
https://www.uhn.ca/PatientsFamilies/Search_Doctors/Pages/doctor_detail.aspx?doctor=615
https://www.ncbi.nlm.nih.gov/gtr/conditions/C3151227/
https://www.malacards.org/card/retinitis_pigmentosa_59
Since having been affected by RP – Retinitis Pigmentosa, a presently progressive form of blindness, Cantor Chaiet is currently registered with the CNIB (Canadian National Institute for the Blind) and the FFB (Foundation Fighting Blindness). Advanced genetic testing and clinical trials for genetic and stem cell therapies are now ongoing and will soon usher in a new era of visual restoration for those with degenerative retinal disorders like RP , AMD (Macular Degeneration) and other associated dystrophies of the retina. http://www.blindness.org/
We are encouraged by this website – a testimonial of Cantor Chaiet’s multi-faceted career, his present challenges and aspirations. We hope it will enrich your own personal quest for vocal excellence as it is updated with medical and ‘musical’ breakthroughs.
The FFFB /Foundation for Fighting Blindness is receiving your generous donations towards finding the cure for Retinal disorders such as RP and AMD … Cures are now in Sight. http://www.blindness.org/
Genetic Testing For Retinal Degenerative Diseases: Information and Resources for Affected Individuals, Families and Health Care Providers
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SCROLL DOWN TO BOTTOM TO VIEW CANTOR CHAIET’S GENETICS REPORT RE:
BLUEPRINT GENETICS CLINICAL REPORT FROM FINLAND
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Current Research
https://www.fightingblindness.org/research/retinitis-pigmentosa-research-advances-3
https://health.ucsd.edu/news/releases/Pages/2017-04-21-crispr-reverses-retinitis-pigmentosa.aspx
https://www.splice-bio.com/the-first-therapeutic-use-of-crispr-may-be-for-retinitis-pigmentosa/
EYE TRANSPLANTATION IS ON THE HORIZON
ARPA-H launches program to restore vision through whole eye transplantation
Project has moonshot goal of curing blindness through whole eye transplantation
https://www.healio.com/news/ophthalmology/20240114/ophthalmologists-invited-to-join
A BRIEF REVIEW OF GENETIC TERMS RELATED TO RETINITIS PIGMENTOSA 59
RARE DISEASES GENETIC DISORDERS
Heterozygous vs. Homozygous: What’s the Difference?
By Ruth Jessen Hickman, MD Updated on August 29, 2022
Medically reviewed by Steffini Stalos, DO
Heterozygous vs Homozygous
Homozygous and heterozygous are words used to describe the pairs of genes you inherited from your parents. If you are homozygous for a particular gene, it means you inherited the same version of that gene from both your mother and father. In Retinitis Pigmentosa 59
the affected person inherited the RP59 gene from both their mother and their father.
If you are heterozygous for a particular gene, it means you inherited two different versions of the gene, one from your mother and one from your father.
For example, if you inherited the gene for blonde hair from your mother and the gene for blonde hair from your father, you are homozygous for the gene that controls hair color. If, however, you inherited the gene for blonde hair from your mother and the gene for brown hair from your father, you are heterozygous for that gene.
Heterozygous vs Homozygous
The words heterozygous and homozygous don’t refer to individual people, but to individual genes. For example, you can be heterozygous for the gene that controls hair color, but homozygous for the gene that controls eye color. This just means that you have two different versions of the hair color gene, and two identical copies of the eye color gene.
Each version or variation of a gene is called an allele. You get one allele from each parent. Sometimes the alleles are identical and sometimes they are different.
When you inherit different alleles, the dominant allele is the one that is expressed in your body. For example, if you are heterozygous for the hair color gene, you might have one copy of the blonde hair allele and one copy of the brown hair allele. Because the brown hair allele is dominant, you will have brown hair.
A person with blonde hair, however, must be homozygous for the hair color gene, because the blonde hair allele is recessive. This means there needs to be two copies of the blonde hair allele in order for that trait to be expressed.
What Is a Gene?
Genes are very specific segments of DNA (deoxyribonucleic acid). Each of your cells contains very long stretches of DNA. This is heritable material that you get from each of your parents.
DNA is composed of a series of individual components called nucleotides. There are four different types of nucleotides in DNA:
Adenine (A)
Guanine (G)
Cytosine (C)
Thymine (T)
Inside the cell, DNA is usually found bundled up into chromosomes (found in 23 different pairs).
Genes are used by other machinery inside the cell to make specific proteins. Proteins are the building blocks used in many critical roles inside the body, including structural support, cell signaling, chemical reaction facilitation, and transport
The cell makes protein (out of its building blocks, amino acids) by reading the sequence of nucleotides found in the DNA. The cell uses a sort of translation system to use information in the DNA to build specific proteins with specific structures and functions.
Specific genes in the body fulfill distinct roles. For example, hemoglobin is a complex protein molecule that works to carry oxygen in the blood. Several different genes (found in the DNA) are used by the cell to make the specific protein shapes needed for this purpose.
You inherit DNA from your parents. Broadly speaking, half of your DNA comes from your mother and the other half from your father. For most genes, you inherit one copy from your mother and one from your father.
However, there is an exception involving a specific pair of chromosomes called sex chromosomes. Because of the way sex chromosomes work, males only inherit a single copy of certain genes.
Variations in Genes
The genetic code of human beings is quite similar: Well over 99 percent of nucleotides that are part of genes are the same across all humans. Alleles, however, have variations in the sequence of nucleotides in specific genes.
For example, one allele might begin with the sequence ATTGCT, and another might begin ACTGCT instead.
Sometimes these variations don’t make a difference in the end protein, but sometimes they do. They might cause a small difference in the protein that makes it work slightly differently.
In this example, a person who is homozygous for this gene would have two copies of the version of the gene beginning “ATTGCT” or two copies of the version beginning “ACTGCT.” A person who is heterozygous for this gene, however, would have one version of the gene beginning “ACTGCT” and also another version of the gene beginning “ATTGCT.”
Homozygous: You inherit the same version of the gene from each parent, so you have two matching genes.
Heterozygous: You inherit a different version of a gene from each parent. They do not match.
Disease Mutations
Many of these mutations aren’t a big deal and just contribute to normal human variation. However, other specific mutations can lead to human disease. That is often what people are talking about when they mention “homozygous” and “heterozygous”: a specific type of mutation that can cause disease.
One example is sickle cell anemia. In sickle cell anemia, there is a mutation in a single nucleotide that causes a change in the nucleotide of a gene (called β-globin gene).1
This causes an important change in the configuration of hemoglobin. Because of this, red blood cells carrying hemoglobin begin to break down prematurely. This can lead to problems like anemia and shortness of breath.
Generally speaking, there are three different possibilities:
Someone is homozygous for the normal β-globin gene (has two normal copies)
Someone is heterozygous (has one normal and one abnormal copy)
Someone is homozygous for the abnormal β-globin gene (has two abnormal copies)
People who are heterozygous for the sickle cell gene have one unaffected copy of the gene (from one parent) and one affected copy of the gene (from the other parent).
These people usually don’t get the symptoms of sickle cell anemia. However, people who are homozygous for the abnormal β-globin gene do get symptoms of sickle cell anemia.
Heterozygotes and Genetic Diseases
A heterozygote is a person who has two different alleles for each of one or more genes. Heterozygotes can get genetic disease, but it depends on the type of disease. In some types of genetic diseases, a heterozygous individual is almost certain to get the disease.
In diseases caused by dominant genes, a person needs only one bad copy of a gene to have problems. One example is the neurological disorder Huntington’s disease.
A person with only one affected gene (inherited from either parent) will still almost certainly get Huntington’s disease as a heterozygote.2 A homozygote who receives two abnormal copies of the disease from both parents would also be affected, but this is less common for dominant disease genes.
For recessive diseases, like sickle cell anemia, heterozygotes do not get the disease. However, sometimes they may have other subtle changes, depending on the disease.
If a dominant gene causes a disease, a heterozygote may manifest the disease. If a recessive gene causes a disease, a heterozygote may not develop the disease or may have lesser effects of it.
What About Sex Chromosomes?
Sex chromosomes are the X and Y chromosomes that play a role in gender differentiation. Women inherit two X chromosomes, one from each parent. So a female can be considered homozygous or heterozygous about a specific trait on the X chromosome.
Men are a little more confusing. They inherit two different sex chromosomes: X and Y. Because these two chromosomes are different, the terms “homozygous” and “heterozygous” don’t apply to these two chromosomes on men.
You may have heard of sex-linked diseases, like Duchenne muscular dystrophy.3 These display a different inheritance pattern than standard recessive or dominant diseases inherited through the other chromosomes (called autosomes).
Heterozygote Advantage
For some disease genes, it is possible that being a heterozygote gives a person certain advantages. For example, it is thought that being a heterozygote for the sickle cell anemia gene may be somewhat protective for malaria, in comparison to people who don’t have an abnormal copy.
Inheritance
Let’s assume two versions of a gene: A and a. When two people have a child, there are several possibilities.
Both parents are AA: All of their children will be AA as well (homozygous for AA).
Both parents are aa: All of their children will be aa as well (homozygous for aa).
One parent is Aa and another parent is Aa: Their child has a 25 percent chance of being AA (homozygous), a 50 percent chance of being Aa (heterozygous), and a 25 percent chance of being aa (homozygous)
One parent is Aa and the other is aa: Their child has a 50 percent chance of being Aa (heterozygous) and a 50 percent chance of being aa (homozygous).
One parent is Aa and the other is AA: Their child has a 50 percent chance of being AA (homozygous) and a 50 percent chance of being Aa (heterozygous).
The study of genetics can be complex. Nevertheles, if a genetic condition runs in your family, don’t hesitate to consult a genetic counselor or your health professional about what this means for you.
The advancement of genetic treatments depends also on you and your family to find protocols and eventually, cures in 2024 onwards.
https://medlineplus.gov/genetics/understanding/testing/benefits/
https://www.fda.gov/consumers/consumer-updates/how-gene-therapy-can-cure-or-treat-diseases
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BLUEPRINT GENETICS REPORT FROM FINLAND FOR CANTOR CHAIET
Blueprint Genetics Oy, Keilaranta 16 A-B, 02150 Espoo, Finland VAT number: FI22307900, CLIA ID
Patient: Chaiet, Stephen Allen, DoB: 1953-02-23 1 / 11
Blueprint Genetics Oy, Keilaranta 16 A-B, 02150 Espoo, Finland VAT number: FI22307900, CLIA ID
Number: 99D2092375, CAP Number: 9257331
1 / 11
Retinal Dystrophy Panel Plus
REFERRING HEALTHCARE PROFESSIONAL
NAME HOSPITAL
Chantal Morel CAN – Ontario – Mount Sinai Hospital
PATIENT
NAME DOB AGE GENDER ORDER ID
Chaiet, Stephen Allen 1953-02-23 69 Male 189771
PRIMARY SAMPLE TYPE SAMPLE COLLECTION DATE CUSTOMER SAMPLE ID
Buccal Swab 2022-05-03 HN: 7070356030 JH, PA#: L20220317 379
SUMMARY OF RESULTS WITH
PRIMARY FINDINGS
The patient is homozygous for DHDDS c.124A>G, p.(Lys42Glu), which is pathogenic.
PRIMARY FINDINGS: SEQUENCE ALTERATIONS
GENE
DHDDS
TRANSCRIPT
NM_024887.3
NOMENCLATURE
c.124A>G, p.(Lys42Glu)
GENOTYPE
HOM
CONSEQUENCE
missense_variant
INHERITANCE Homozygous
AR autosomal recessive retinitis pigmentosa 59
CLASSIFICATION
Pathogenic
ID
rs147394623
ASSEMBLY
GRCh37/hg19
POS
1:26764719
REF/ALT
A/G
gnomAD AC/AN
63/282892
POLYPHEN
benign
SIFT
deleterious
MUTTASTER
disease causing
PHENOTYPE
Developmental delay and seizures with or without movement abnormalities (DEDSM),
Retinitis pigmentosa
SEQUENCING PERFORMANCE METRICS
PANEL GENES EXONS / REGIONS BASES BASES > 20X MEDIAN
COVERAGE
PERCENT
> 20X
Retinal Dystrophy Panel 314 4998 989155 988183 211 99.9
PANEL GENES EXONS / REGIONS BASES BASES > 1000X MEDIAN
COVERAGE
PERCENT
> 1000X
Mitochondrial genome 37 – 15358 15358 9603 100
TARGET REGION AND GENE LIST
The Blueprint Genetics Retinal Dystrophy Panel (version 7, Oct 30, 2021) Plus Analysis includes sequence analysis and copy
number variation analysis of the following genes: ABCA4, ABCC6*, ABCD1*, ABHD12, ACO2, ADAM9, ADAMTS18, ADGRV1,
ADIPOR1*, AGBL5, AHI1, AIPL1, ALMS1*, AMACR, ARHGEF18, ARL13B, ARL2BP, ARL3, ARL6, ARMC9, ARR3, ARSG, ATF6, ATOH7,
B9D1, B9D2, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BEST1, C1QTNF5, C21ORF2, C2ORF71, C5ORF42,
Patient: Chaiet, Stephen Allen, DoB: 1953-02-23 2 / 11
Blueprint Genetics Oy, Keilaranta 16 A-B, 02150 Espoo, Finland VAT number: FI22307900, CLIA ID
Number: 99D2092375, CAP Number: 9257331
2 / 11
C8ORF37, CA4, CABP4, CACNA1F, CACNA2D4, CAPN5, CC2D2A#, CDH23, CDH3, CDHR1, CEP104, CEP120, CEP164, CEP19,
CEP250, CEP290*, CEP41, CEP78, CEP83, CERKL, CHM#, CIB2, CISD2*, CLN3, CLN5, CLN6, CLN8, CLRN1, CNGA1#, CNGA3, CNGB1,
CNGB3, CNNM4, COL11A1, COL11A2, COL18A1, COL2A1, COL9A1, COL9A2, COL9A3, COQ2, CPE, CRB1, CRX, CSPP1, CTC1,
CTNNA1, CTNNB1, CTSD, CWC27, CYP4V2, DFNB31, DHDDS, DHX38, DNAJC5, DRAM2, DTHD1, DYNC2H1, EFEMP1, ELOVL4,
EMC1, ESPN*, EXOSC2, EYS*, FAM161A, FDXR, FLVCR1, FRMD7, FZD4, GNAT1, GNAT2, GNB3, GNPTG, GPR143, GPR179, GRK1,
GRM6, GUCA1A, GUCY2D, HARS, HGSNAT, HK1#, HMX1, IDH3A, IDH3B, IFT140, IFT172, IFT27, IFT81#, IMPDH1, IMPG1, IMPG2,
INPP5E, INVS, IQCB1, ISPD, JAG1, KCNJ13, KCNV2, KIAA0556, KIAA0586#, KIAA0753, KIAA1549, KIF11, KIF7, KIZ, KLHL7, LAMA1,
LCA5, LRAT, LRIT3, LRP2, LRP5*, LZTFL1, MAK, MERTK, MFN2, MFRP, MFSD8, MKKS, MKS1, MMACHC, MT-ATP6, MT-ATP8, MT-CO1,
MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6, MT-RNR1, MT-RNR2, MT-TA, MT-TC,
MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MTTT,
MT-TV, MT-TW, MT-TY, MTTP, MVK, MYO7A, NAGLU, NDP, NEK2#, NMNAT1#, NPHP1, NPHP3, NPHP4, NR2E3, NR2F1, NRL, NYX,
OAT, OCA2, OFD1, OPA1, OPA3, OPN1SW, OTX2, P3H2, PANK2, PAX2, PCDH15, PCYT1A, PDE6A, PDE6B, PDE6C, PDE6D, PDE6G,
PDE6H, PDSS1#, PDSS2, PDZD7#, PEX1, PEX10, PEX11B, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6,
PEX7, PHYH, PISD, PITPNM3, PLA2G5, PLK4, PNPLA6, POC1B, POMGNT1, PPT1, PRCD, PRDM13, PROM1, PRPF3, PRPF31, PRPF4,
PRPF6, PRPF8, PRPH2, PRPS1*, RAB28, RAX2, RBP3, RBP4, RCBTB1, RD3, RDH11, RDH12, RDH5, REEP6, RGR, RGS9, RGS9BP,
RHO, RIMS1, RLBP1, ROM1, RP1, RP1L1, RP2, RPE65, RPGR, RPGRIP1, RPGRIP1L#, RS1, RTN4IP1, SAG, SAMD11, SCAPER, SCLT1#,
SDCCAG8, SEMA4A, SGSH, SLC24A1, SLC25A46, SLC45A2, SLC7A14, SNRNP200, SPATA7, SPP2, SRD5A3*, TCTN1#, TCTN2,
TCTN3, TEAD1, TIMM8A*, TIMP3, TMEM107, TMEM126A, TMEM138, TMEM216, TMEM231, TMEM237, TMEM67, TOPORS, TPP1,
TRAF3IP1, TREX1, TRIM32, TRPM1, TSPAN12, TTC21B, TTC8, TTLL5, TTPA, TUB, TUBB4B, TUBGCP4, TUBGCP6, TULP1, TYR*,
TYRP1, USH1C, USH1G, USH2A, VCAN, VPS13B, WDPCP, WDR19, WFS1, YME1L1*, ZNF408, ZNF423 and ZNF513. The following
exons are not included in the panel as they are not covered with sufficient high quality sequence reads: CC2D2A (NM_020785:7),
CHM (NM_001145414:5), CNGA1 (NM_001142564:2), HK1 (NM_001322365:5), IFT81 (NM_031473:12), KIAA0586
(NM_001244189:6, 33), NEK2 (NM_001204182:8), NMNAT1 (NM_001297779:5), PDSS1 (NM_014317:2), PDZD7 (NM_024895:10),
RPGRIP1L (NM_015272:23), SCLT1 (NM_001300898:6) and TCTN1 (NM_001173976:2;NM_024549:6).
*Some, or all, of the gene is duplicated in the genome. Read more: https://blueprintgenetics.com/pseudogene/
#The gene has suboptimal coverage when >90% of the gene’s target nucleotides are not covered at >20x with a mapping
quality score of MQ>20 reads.
The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#).
STATEMENT
CLINICAL HISTORY
Patient is a 69-year-old male with clinical suspicion of retinitis pigmentosa, presenting with peripheral vision loss, nyctalopia,
cataracts, and photophobia. . Ethnicity: Polish, Russian. Ashkenazi Jewish.
Family history: Brother was diagnosed with retinitis pigmentosa in his 20s. Parents are non-consanguineous.
CLINICAL REPORT
Sequence analysis using the Blueprint Genetics (BpG) Retinal Dystrophy Panel identified a homozygous missense variant DHDDS
c.124A>G, p.(Lys42Glu).
DHDDS c.124A>G p.(Lys42Glu)
There are 63 individuals heterozygous for this variant in gnomAD, a large reference population database (n>120,000 exomes
and >15,000 genomes) which aims to exclude individuals with severe pediatric disease. The variant affects a highly conserved
amino acid in the decaprenyl diphosphate synthase-like domain of the protein, there is small physicochemical difference
Patient: Chaiet, Stephen Allen, DoB: 1953-02-23 3 / 11
Blueprint Genetics Oy, Keilaranta 16 A-B, 02150 Espoo, Finland VAT number: FI22307900, CLIA ID
Number: 99D2092375, CAP Number: 9257331
3 / 11
between Lys and Glu (Grantham score 56, [0-215]), and most in silico tools utilized predict the alteration to be deleterious.
The DHDDS c.124A>G, p.(Lys42Glu) variant is a founder variant in Ashkenazi Jewish population associated with autosomal
recessive retinitis pigmentosa (RP; PMID: 21295282, 21295283, 28130426, 24664694; ClinVar ID 30709). In a recent study,
the DHDDS p.(Lys42Glu) variant explained 12.2% of the RP in a cohort of 230 Ashkenazi Jewish families with RP. Patients
harboring a variant in DHDDS demonstrated fundus findings at a relatively early age and major loss of VA seemed to occur
during the third and fourth decades of life (PMID: 29276052).
DHDDS
The DHDDS gene (MIM *608172) on chromosome 1p36.11 encodes dehydrodolichyl diphosphate synthase, which catalyzes cisprenyl
chain elongation to produce the polyprenyl backbone of dolichol, a glycosyl carrier lipid required for the biosynthesis of
several classes of glycoproteins. Variants in this gene have been associated with three different phenotypes, developmental
delay and seizures with or without movement abnormalities (DEDSM, MIM #617836), retinitis pigmentosa 59 (RP59, MIM
#613861) and congenital disorder of glycosylation, type 1bb (CDG1BB, MIM #613861).
DEDSM is a rare autosomal dominant neurodevelopmental disorder characterized by global developmental delay, variable
intellectual disability, and early-onset seizures with a myoclonic component. Most patients have delayed motor development and
show abnormal movements, including ataxia, dystonia, and tremor (PMID: 29100083). Two different de novo missense variants
in DHDDS have been reported in five unrelated patients (PMID: 29100083).
RP59 is a rare autosomal recessive nonsyndromic retinal dystrophy. It has been shown that patients with RP59 had abnormal
serum and urine dolichols (PMID: 24078709, 27343064). Four missense variants have been reported in association with RP59
(PMID: 21295282, 28454995, 24078709, 29276052). The missense variant DHDDS c.124A>G, p.(Lys42Glu) is a founder mutation
in Ashkenazi Jewish population. The DHDDS is not a major RP gene in other populations (PMID: 29276052).
In addition, one patient with biallelic loss of function variants (nonsense and splice site) in DHDDS has been reported to have a
fatal multisystem disorder, annotated on OMIM as Congenital disorder of glycosylation, type 1bb (MIM #613861, PMID:
27343064). This patient had intrauterine growth retardation, axial hypotonia, peripheral hypertonia, renal failure, seizures and
senorineural deafness. However, the association between biallelic variants in DHDDS and this particular phenotype remains to be
fully established.
Mutation nomenclature is based on GenBank accession NM_024887.3 (DHDDS) with nucleotide one being the first nucleotide of
the translation initiation codon ATG.
CONCLUSION
DHDDS c.124A>G, p.(Lys42Glu) is classified as pathogenic, based on currently available evidence supporting its disease-causing
role. Retinitis pigmentosa caused by DHDDS variants is inherited in an autosomal recessive manner. The patient is homozygous
for the variant, which is consistent with autosomal recessive inheritance. If the patient’s parents are each confirmed to be
carriers of this variant, any siblings of the patient will have a 25% chance of being homozygous for the variant and thus affected,
a 50% chance of being an asymptomatic carrier, and a 25% chance of being an unaffected non-carrier. Genetic counseling and
family member testing are recommended.
STEP DATE
Order date Mar 17, 2022
Sample received May 09, 2022
Sample in analysis May 10, 2022
Reported Jun 03, 2022
Patient: Chaiet, Stephen Allen, DoB: 1953-02-23 4 / 11
Blueprint Genetics Oy, Keilaranta 16 A-B, 02150 Espoo, Finland VAT number: FI22307900, CLIA ID
Number: 99D2092375, CAP Number: 9257331
4 / 11
On Jun 03, 2022 the statement has been prepared by our geneticists and physicians, who have together evaluated the
sequencing results:
Marta Gandía, Ph.D.
Geneticist
Juha Koskenvuo, MD, Ph.D.
Lab Director, Chief Medical Officer
Recap:
Cantor Stephen Chaiet’s Retinal Physicians :
Dr. Keyvan Koushan https://www.torontoretinainstitute.com/dr-koushan.html#/
Dr. Nupura Bakshi https://www.youtube.com/watch?v=ZqjFwOYrs1w
Dr. Stephen Dorrepaal https://clarityeye.ca/doctors/stephen-dorrepaal/
Updates to come
The Singer's Voice Cantor Stephen Chaiet 