title: Prenatal genotyping of four common oculocutaneous albinism genes in 51 Chinese families.
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 the TYR 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.
authors.affiliation: Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: weiaihua3000@163.com.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Dong-Jie
authors.initials: DJ
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; Center for Medical Genetics, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address: wli@genetics.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000483:Alleles; D000951:Antigens, Neoplasm / Q000235:genetics; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D011247:Pregnancy
chemical_list: D000951:Antigens, Neoplasm; C102160:HPS1 protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C510061:SLC45A2 protein, human
keywords: Genotype; Hermansky–Pudlak syndrome; Oculocutaneous albinism; Prenatal genetic testing; Previously unidentified allele