回旋状脉络膜视网膜萎缩一家系的新型突变与临床观察

目的：探讨一个回旋状脉络膜视网膜萎缩(GA)中国家系各家庭成员OAT基因的致病性突变及临床表现。

方法：对该家系中的6名家庭成员均进行详细的眼科检查，通过全外显子组测序、生物信息学分析及Sanger验证明确基因测序结果及致病性突变。

结果：先证者因其临床表现及体征诊断为GA。全外显子组测序结果显示先证者OAT基因分别于第6外显子和第10外显子上发现致病突变c.722C>T(p.P241L)、c.1186C>T(p.R396X)，该复合杂合性突变在家系中呈现共分离状态。先证者的父亲和哥哥均检出杂合型p.R396X致病变异，母亲检出杂合型p.P241L致病变异。除先证者外，其他家庭成员均无临床症状。

结论：该家系的先证者为复合杂合性突变，其中p.P241L为首次报道的基因突变类型。这一研究结果扩大了OAT基因变异的范围，有利于在分子基础水平进一步理解GA的致病因素。新型突变类型的发现与证实也将有助于为GA的临床诊断和基因治疗提供新的依据。

Novel gene mutation and clinical features in a family with gyrate atrophy of choroid and retina

AIM: To investigate the pathogenic mutations of the OAT gene in a Chinese family affected with gyrate atrophy of choroid and retina(GA)and describe their clinical manifestations.

METHODS: All available family members have underwent detailed ophthalmological examinations. The sequencing results and pathogenic mutations were clarified by whole exome sequencing, bioinformatics analysis and Sanger sequencing.

RESULTS: Based on the clinical manifestations and symptoms, the proband was diagnosed with GA. A missense mutation of c.722C>T(p.P241L)in exon 6 and a nonsense mutation of c.1186C>T(p.R396X)in exon 10 were identified in the OAT gene of the proband, which was a compound heterozygotic mutation. This compound heterozygous mutation showed co-segregation in the family. The heterozygous pathogenic variant of p.R396X was detected in both the proband''s father and elder brother, and the heterozygous pathogenic variant of p.P241L was detected in proband''s mother. Except for the proband, no other family members have abnormal clinical manifestations.

CONCLUSION: The proband of this family is a compound heterozygous mutation, in which p.P241L is the first reported gene mutation type. This result expands the range of OAT gene variation and is conducive to further understanding the pathogenic factors of GA at the molecular basis level. The discovery and confirmation of the novel mutation type will also help to provide a new basis for the clinical diagnosis and gene therapy of GA.