NGS-based targeted sequencing identified two novel variants in Southwestern Chinese families with oculocutaneous albinism.
Medical genomics
Nucleotide variations
OCA2
Oculocutaneous albinism
TYR
Targeted NGS
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
29 Apr 2022
29 Apr 2022
Historique:
received:
09
11
2021
accepted:
27
04
2022
entrez:
29
4
2022
pubmed:
30
4
2022
medline:
4
5
2022
Statut:
epublish
Résumé
Oculocutaneous albinism (OCA) is a group of heterogeneous genetic diseases characterized by a reduction or complete lack of pigmentation in the hair, skin, and eyes. It is associated with reduced visual acuity, nystagmus, photophobia, and strabismus. OCA type 1 (OCA1) and type 2 (OCA2) are caused by mutations in the tyrosinase (TYR) and OCA2 genes, which are responsible for most cases of OCA. The present study aimed to identify the mutational spectra of 18 southwest Chinese probands with OCA. We used a skin disease-targeted panel to sequence more than 400 genes, including 23 genes (TYR, OCA2, AP3B1, BLOC1S3, BLOC1S6, C10orf11, DTNBP1, FRMD7, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, LYST, MC1R, MITF, MLPH, MYO5A, RAB27A, SLC24A5, SLC45A2, TYRP1) associated with syndromic and non-syndromic albinism. The targeted panel was applied to 18 patients from southwest China, nine (50%) patients were diagnosed with OCA1, and nine (50%) were diagnosed with OCA2. Our data indicate that OCA1 and OCA2, the most common subtypes, probably have the same prevalence in southwest China. In total, we identified 26 variants in TYR and OCA2 from 18 OCA cases using the NGS technology, including 24 variants presented in the Human Gene Mutation Database Professional (HGMD) and two novel variants, c.559_560insCATTATTATGTGTCAAATTATCCCC in TYR and c.1514 T > C in OCA2, which have not been previously reported. According to the American College of Medical Genetics and Genomics (ACMG) classification, c.559_560insCATTATTATGTGTCAAATTATCCCC (p.G190Cfs*12) is classified as a pathogenic variant, and c.1514 T > C (p.F505S) is evaluated as a likely pathogenic variant. Two novel variants were identified which will expand the mutational spectra of TYR and OCA2. The results of the present study may have implications for genetic counseling, carrier screening, and clinical management of the disease.
Sections du résumé
BACKGROUND
BACKGROUND
Oculocutaneous albinism (OCA) is a group of heterogeneous genetic diseases characterized by a reduction or complete lack of pigmentation in the hair, skin, and eyes. It is associated with reduced visual acuity, nystagmus, photophobia, and strabismus. OCA type 1 (OCA1) and type 2 (OCA2) are caused by mutations in the tyrosinase (TYR) and OCA2 genes, which are responsible for most cases of OCA. The present study aimed to identify the mutational spectra of 18 southwest Chinese probands with OCA.
RESULTS
RESULTS
We used a skin disease-targeted panel to sequence more than 400 genes, including 23 genes (TYR, OCA2, AP3B1, BLOC1S3, BLOC1S6, C10orf11, DTNBP1, FRMD7, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, LYST, MC1R, MITF, MLPH, MYO5A, RAB27A, SLC24A5, SLC45A2, TYRP1) associated with syndromic and non-syndromic albinism. The targeted panel was applied to 18 patients from southwest China, nine (50%) patients were diagnosed with OCA1, and nine (50%) were diagnosed with OCA2. Our data indicate that OCA1 and OCA2, the most common subtypes, probably have the same prevalence in southwest China. In total, we identified 26 variants in TYR and OCA2 from 18 OCA cases using the NGS technology, including 24 variants presented in the Human Gene Mutation Database Professional (HGMD) and two novel variants, c.559_560insCATTATTATGTGTCAAATTATCCCC in TYR and c.1514 T > C in OCA2, which have not been previously reported. According to the American College of Medical Genetics and Genomics (ACMG) classification, c.559_560insCATTATTATGTGTCAAATTATCCCC (p.G190Cfs*12) is classified as a pathogenic variant, and c.1514 T > C (p.F505S) is evaluated as a likely pathogenic variant.
CONCLUSIONS
CONCLUSIONS
Two novel variants were identified which will expand the mutational spectra of TYR and OCA2. The results of the present study may have implications for genetic counseling, carrier screening, and clinical management of the disease.
Identifiants
pubmed: 35488210
doi: 10.1186/s12864-022-08597-3
pii: 10.1186/s12864-022-08597-3
pmc: PMC9055679
doi:
Substances chimiques
Cytoskeletal Proteins
0
FRMD7 protein, human
0
Membrane Proteins
0
Membrane Transport Proteins
0
Monophenol Monooxygenase
EC 1.14.18.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
332Subventions
Organisme : National Natural Science Foundation of China
ID : 82003358
Organisme : Science and Technology Department of Sichuan Province
ID : 2021YFS0078
Organisme : National Key Research and Development Program of China
ID : 2021YFC1005300
Informations de copyright
© 2022. The Author(s).
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