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 no...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-1w4,6,7）,and ten genes for syndromic OCA（HPS-1e9,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（Hermanskye 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.C112 R,p.H363 R and p.G379 V of TYR） and one in-frame deletional PUA（p.S222 del of SLC24A5） led to fetuses with OCA when co-inherited with other disease causative alleles.Three PUAs（p.P152 H and p.W272 X of TYR,p.A486 T 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.Q83 X and p.A658 T of TYR,p.G161 R and p.G366 R of SLC24A5） did not transmit to the unaffected fetuses.In addition,the in vitro transfection assays showed that the p.S192 Y 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.展开更多
基金partially supported by grants from the National Natural Science Foundation of China(Nos.81472871 and31230046)the Natural Science Foundation of Beijing(No.7132073)the State Key Laboratory of Molecular Developmental Biology of China(No.2013-MDB-KF-03)
文摘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-1w4,6,7）,and ten genes for syndromic OCA（HPS-1e9,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（Hermanskye 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.C112 R,p.H363 R and p.G379 V of TYR） and one in-frame deletional PUA（p.S222 del of SLC24A5） led to fetuses with OCA when co-inherited with other disease causative alleles.Three PUAs（p.P152 H and p.W272 X of TYR,p.A486 T 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.Q83 X and p.A658 T of TYR,p.G161 R and p.G366 R of SLC24A5） did not transmit to the unaffected fetuses.In addition,the in vitro transfection assays showed that the p.S192 Y 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.
