Sjogren-Larsson综合征患儿的 ALDH3A2基因变异遗传学分析并文献复习  

Genetic analysis of ALDH3A2 gene variation in children with Sjogren-Larsson syndrome and literature review

作　　者：焦莹 强荣 王林 张钰琦 Jiao Ying;Qiang Rong;Wang Lin;Zhang Yuqi(Center of Medical Genetics,Northwest Women’s and Children’s Hospital,Xi’an 710061,China)

机构地区：[1]西安市曲江新区西北妇女儿童医院遗传中心,西安710061

出　　处：《国际遗传学杂志》2024年第4期331-338,共8页International Journal of Genetics

摘　　要：目的探讨国内Sjogren-Larsson综合征(Sjogren-Larsson syndrome,SLS)患儿的基因变异及临床表型特征。方法回顾性分析1例以鱼鳞病、双下肢痉挛起病的SLS综合征患儿临床资料,并对国内已报道相关文献进行复习归纳。结果患儿,女,10岁,鱼鳞病、全面发育落后、双下肢痉挛性截瘫、脊柱侧弯、视力低下、牙釉质发育不良等,核磁共振成像(MRI)平扫显示脑白质脱髓鞘及脑白质区域T2W1高信号。全外显子组检测提示患儿ALDH3A2基因c.1157A>G(p.Asn386Ser)、c.421dup(p.Glu141Glyfs*24)杂合变异,分别父母来源,根据ACMG评级标准,均评级为致病性。经文献复习,国内SLS患儿主要由ALDH3A2基因复合杂合变异所致(占比65%),以c.1157A>G变异频率最高(89.5%),且临床表现以鱼鳞病、语言障碍、运动发育落后并MRI检查异常为最主要临床表现。结论ALDH3A2基因c.1157A>G和c.421dup复合杂合变异可以解释本例患儿临床表现。此外,本研究归纳总结了国内SLS患儿的ALDH3A2基因变异及临床表现频率;对出生鱼鳞病的早产儿尽早关注并检测ALDH3A2基因,对后续治疗及预后评估具有重要临床指导价值。ObjectiveTo investigate the gene variation and clinical phenotype of Sjogren-Larsson syndrome(SLS)in China.MethodsA case of SLS with ichthyosis and spasticity of lower limbs was analyzed retrospectively.And the domestic reported literature were reviewed and summarized.ResultsThe patient was a 10-year-old female with ichthyosis,hypoplasia,spastic paraplegia of lower limbs,scoliosis,poor vision,enamel hypoplasia,etc.The magnetic resonance imagine(MRI)scan showed demyelination and high T2W1 signal in the white matter.Genetic testing found that there were two heterozygous mutation sites,c.1157A>G(p.Asn386Ser)and c.421dup(p.Glu141Glyfs*24),in the ALDH3A2 gene which were rated as pathogenic to the ACMG guideline.According to the literature review,the main cause of SLS in China was compound heterozygous variant of ALDH3A2 gene(65%),and the frequency of c.1157A>G variant was the highest(89.5%).Moreover,and the main clinical manifestations were ichthyosis,language disorder,motor retardation and MRI abnormality.ConclusionThe compound heterozygous variant of c.1157A>G and c.421dup in ALDH3A2 gene may explain the clinical manifestation of this case,in which the c.421dup variant was first reported in China and abroad.In addition,this study summarized the ALDH3A2 gene variation and clinical manifestation frequency of SLS in China.Particularly,paid attention to the premature infants with ichthyosis and detected the ALDH3A2 gene as early as possible,it has important clinical guiding value for follow-up treatment and prognosis evaluation.

关 键 词：Sjogren-Larsson综合征 ALDH3A2基因 鱼鳞病 痉挛性截瘫 发育迟缓 

分 类 号：R725.9[医药卫生—儿科]