Genetic analysis and prenatal diagnosis of 20 Chinese families with oculocutaneous albinism.
Adolescent
Adult
Albinism, Oculocutaneous
/ diagnosis
Amniocentesis
Asian People
/ genetics
Child
Female
Genetic Counseling
Humans
Infant, Newborn
Male
Membrane Proteins
/ genetics
Membrane Transport Proteins
/ genetics
Middle Aged
Monophenol Monooxygenase
/ genetics
Noninvasive Prenatal Testing
/ methods
Pedigree
Pregnancy
Exome Sequencing
HPS1
TYR
OCA
prenatal diagnosis
whole exome sequencing
Journal
Journal of clinical laboratory analysis
ISSN: 1098-2825
Titre abrégé: J Clin Lab Anal
Pays: United States
ID NLM: 8801384
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
12
07
2020
revised:
09
10
2020
accepted:
11
10
2020
pubmed:
31
10
2020
medline:
30
10
2021
entrez:
30
10
2020
Statut:
ppublish
Résumé
Oculocutaneous albinism (OCA) is a group of heterogeneous genetic disorders characterized by abnormal melanin synthesis in the hair, skin, and eyes. OCA exhibits obvious genetic and phenotypic heterogeneity. Molecular diagnosis of causal genes can be of help in the classification of OCA subtypes and the study of OCA pathogenesis． METHODS: In this study, Sanger sequencing and whole exome sequencing were used to genetically diagnose 20 nonconsanguineous Chinese OCA patients. In addition, prenatal diagnosis was provided to six OCA families. Variants of TYR, OCA2, and HPS1 were detected in 85%, 10%, and 5% of affected patients, respectively. A total of 21 distinct variants of these three genes were identified. Exons 1 and 2 were the hotspot regions of the TYR variants, and c.895C > A and c.896G > A were the hotspot variants. We also found seven novel variants: c.731G > A, c.741C > A, c.867C > A, and c.1037-2A > T in TYR, c.695dupT and c.1054A > G in OCA2, and c.9C > A in HPS1. Genetic tests on six fetuses revealed three carrier fetuses, two normal fetuses, and one affected fetus. The follow-up results after birth were consistent with the results of prenatal diagnosis (one fetus terminated during pregnancy was not followed up). This study expands our understanding of the genotypic spectrum of the Chinese OCA population. The findings indicate that prenatal diagnosis can provide important information for genetic counseling.
Sections du résumé
BACKGROUND
BACKGROUND
Oculocutaneous albinism (OCA) is a group of heterogeneous genetic disorders characterized by abnormal melanin synthesis in the hair, skin, and eyes. OCA exhibits obvious genetic and phenotypic heterogeneity. Molecular diagnosis of causal genes can be of help in the classification of OCA subtypes and the study of OCA pathogenesis． METHODS: In this study, Sanger sequencing and whole exome sequencing were used to genetically diagnose 20 nonconsanguineous Chinese OCA patients. In addition, prenatal diagnosis was provided to six OCA families.
RESULTS
RESULTS
Variants of TYR, OCA2, and HPS1 were detected in 85%, 10%, and 5% of affected patients, respectively. A total of 21 distinct variants of these three genes were identified. Exons 1 and 2 were the hotspot regions of the TYR variants, and c.895C > A and c.896G > A were the hotspot variants. We also found seven novel variants: c.731G > A, c.741C > A, c.867C > A, and c.1037-2A > T in TYR, c.695dupT and c.1054A > G in OCA2, and c.9C > A in HPS1. Genetic tests on six fetuses revealed three carrier fetuses, two normal fetuses, and one affected fetus. The follow-up results after birth were consistent with the results of prenatal diagnosis (one fetus terminated during pregnancy was not followed up).
CONCLUSIONS
CONCLUSIONS
This study expands our understanding of the genotypic spectrum of the Chinese OCA population. The findings indicate that prenatal diagnosis can provide important information for genetic counseling.
Identifiants
pubmed: 33124154
doi: 10.1002/jcla.23647
pmc: PMC7891544
doi:
Substances chimiques
HPS1 protein, human
0
Membrane Proteins
0
Membrane Transport Proteins
0
OCA2 protein, human
0
Monophenol Monooxygenase
EC 1.14.18.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23647Subventions
Organisme : Medical and Health Science and Technology Project of Zhejiang Province support plan
ID : 2020KY921
Organisme : Science and Technology Planning Project of Wenzhou
ID : ZS2017004.
Informations de copyright
© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.
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