Novel compound heterozygous mutations in OCA2 gene associated with non-syndromic oculocutaneous albinism in a Chinese Han patient: a case report
| Autor: | Jing Wang, Jingjing Xu, Yang Wan, Yun Yang, Liangwei Mao, Shuyang Gao, Hai-rong Wang, Hao Li |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Models Molecular 0301 basic medicine Proband genetic structures Protein Conformation Usher syndrome Case Report Gross deletion 030105 genetics & heredity medicine.disease_cause Compound heterozygosity Sequence Analysis Protein Genetics (clinical) Sequence Deletion Genetics OCA2 Sanger sequencing Mutation Targeted NGS High-Throughput Nucleotide Sequencing Exons Oculocutaneous albinism Albinism Oculocutaneous Myosin VIIa symbols Heterozygote lcsh:Internal medicine lcsh:QH426-470 Genetic Counseling Myosins Biology 03 medical and health sciences symbols.namesake Non-syndromic Asian People medicine Humans Genetic Predisposition to Disease lcsh:RC31-1245 Genetic heterogeneity Infant Membrane Transport Proteins medicine.disease lcsh:Genetics 030104 developmental biology |
| Zdroj: | BMC Medical Genetics, Vol 20, Iss 1, Pp 1-6 (2019) BMC Medical Genetics |
| ISSN: | 1471-2350 |
| DOI: | 10.1186/s12881-019-0850-7 |
| Popis: | Background Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders. The present study aimed to identify the genetic cause of a Chinese Han family with non-syndromic oculocutaneous albinism (OCA). Case presentation Here, we report an 11-month-old male proband from a Chinese Han non-consanguineous family, who presented with milky skin, yellow white hair, nystagmus, astigmatism, and hypermetropia. We performed the targeted next-generation sequencing (NGS) on the proband and identified two novel compound heterozygous variants (c.1865 T > C (p.Leu622Pro) and exons 17–21 deletion) in OCA2 gene associated with OCA type 2 (OCA2, OMIM 203200). Meanwhile, a previously reported heterozygous mutation (c.4805G > A) in MYO7 gene related with Usher syndrome type 1B was found. The online tools SIFT, PolyPhen-2, and Mutation Taster predicted variant c.1865 T > C was probably damaging. The residue p.Leu622 was in a highly conserved region among species by CLUSTALW. Three-dimensional homology model with I-TASSER indicated that p.Leu622Pro variant disturbed the formation of the α-helix, resulting in a random coil structure. The gross deletion (exons 17–21) in OCA2 gene has was not been reported previously. These two novel variants in OCA2 gene were inherited from each parent respectively, after verification by Sanger sequencing and quantitative PCR (qPCR) in the family. Conclusions This study indicates the two novel compound heterozygous mutations in OCA2 gene may be responsible for clinical manifestations of OCA2. It expands the mutation spectrum of OCA2 gene and is helpful to screen for large deletions with targeted NGS protocol in monogenic disease. It also assists the genetic counselling, carrier screening and personalized healthcare of the disease. Electronic supplementary material The online version of this article (10.1186/s12881-019-0850-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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