Prenatal Genotyping of Four Common Oculocutaneous Albinism Genes in 51 Chinese Families

Ai-Hua Wei^{a, b
, ,},
Dong-Jie Zang^b,
Zhao Zhang^b,
Xiu-Min Yang^a,
Wei Li^{b, c
, ,}

a.
Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
b.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
c.
Center for Medical Genetics, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China

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Corresponding author: E-mail address: weiaihua3000@163.com (Ai-Hua Wei); E-mail address: wli@genetics.ac.cn (Wei Li)

摘要

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Abstract: Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypopigmentation in eyes, hair and skin, accompanied with vision loss. Currently, six genes have been identified as causative genes for non-syndromic OCA (OCA-1∼4, 6, 7), and ten genes for syndromic OCA (HPS-1–9, CHS-1). Genetic counseling of 51 Chinese OCA families (39 OCA-1 with mutations in theTYR gene, 6 OCA-2 with mutations in the OCA2 gene, 4 OCA-4 with mutations in the SLC45A2 gene, 1 HPS-1 (Hermansky–Pudlak syndrome-1) with mutation in the HPS1 gene, and 1 mixed OCA-1 and OCA-4) led us to perform the prenatal genetic testing of OCA using amniotic fluid cells through the implementation of our optimized strategy. In our cohort, eleven previously unidentified alleles (PUAs) (5 in TYR, 2 in OCA2, and 4 in SLC45A2) were found. Three missense PUAs (p.C112R, p.H363R and p.G379V of TYR) and one in-frame deletional PUA (p.S222del of SLC24A5) led to fetuses with OCA when co-inherited with other disease causative alleles. Three PUAs (p.P152H and p.W272X of TYR, p.A486T of SLC24A5) identified in the OCA probands did not co-transmit with known pathological alleles and thus gave rise to unaffected fetuses. Four PUAs (p.Q83X and p.A658T of TYR, p.G161R and p.G366R of SLC24A5) did not transmit to the unaffected fetuses. In addition, the in vitro transfection assays showed that the p.S192Y variant of TYR produced less pigment compared to the wild-type allele. A fetus with a digenic carrier of OCA-1 and OCA-4 was unaffected. In combination with functional assays, the family inheritance pattern is useful for the evaluation of pathogenicity of PUAs and genetic counseling of OCA.
- Oculocutaneous albinism /
- Prenatal genetic testing /
- Hermansky–Pudlak syndrome /
- Genotype /
- Previously unidentified allele

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参考文献(23)

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doi: 10.1016/j.jgg.2015.05.001

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Prenatal Genotyping of Four Common Oculocutaneous Albinism Genes in 51 Chinese Families

Corresponding author: E-mail address: weiaihua3000@163.com (Ai-Hua Wei); E-mail address: wli@genetics.ac.cn (Wei Li)

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doi: 10.1016/j.jgg.2015.05.001

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Prenatal Genotyping of Four Common Oculocutaneous Albinism Genes in 51 Chinese Families

Corresponding author: E-mail address: weiaihua3000@163.com (Ai-Hua Wei); E-mail address: wli@genetics.ac.cn (Wei Li)

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