一例ALOX12B基因复合杂合变异所致常染色体隐性先天性鱼鳞病的临床及遗传学分析  

Clinical and genetic analysis of a patient with autosomal recessive congenital ichthyosis due to compound heterozygous variants of ALOX12B gene

作　　者：李丹[1] 邓梅[1] Liao Phoebe 宋元宗[1] Li Dan;Deng Mei;Liao Phoebe;Song Yuanzong(Department of Pediatrics,the First Affiliated Hospital of Jinan University,Guangzhou,Guangdong 510630,China)

机构地区：[1]暨南大学附属第一医院儿科,广州510630

出　　处：《中华医学遗传学杂志》2022年第3期321-324,共4页Chinese Journal of Medical Genetics

摘　　要：目的研究1例常染色体隐性先天性鱼鳞病(autosomal recessive congenital ichthyosis,ARCI)患儿的临床和遗传学特征。方法收集和分析1例疑诊ARCI患儿的临床资料,并以病例报告形式描述研究结果。采集患儿与其父母的静脉血,提取基因组DNA后通过二代测序查找病因,Sanger测序验证阳性发现,然后应用Mutation Taster、PROVEN、PolyPhen2等软件预测变异致病性,并根据美国医学遗传学与基因组学学会标准和指南对变异进行分类。结果患儿为1个月7日龄男婴,全身皮肤潮红,附着细碎鳞屑。二代测序表明患儿为ALOX12B基因父源性变异c.1579G>A(p.Val527Met)和母源性变异c.923T>C(p.Leu308Pro)的复合杂合子。前者为已报道的可能致病变异,而后者未见文献报道,生物信息学软件推测其为有害变异。根据ACMG标准和指南,c.923T>C被分类为"可能致病"变异。根据临床和遗传学发现,患者确诊为ARCI。结论ALOX12B基因c.1579G>A和c.923T>C变异为该患儿的致病原因。本研究结果扩展了ALOX12B基因变异谱,为患者的分子诊断及其家庭的遗传咨询和产前诊断提供了分子标记物。Objective To explore the clinical and genetic characteristics of a pediatric patient suspected for Autosomal Recessive Congenital Ichthyosis(ARCI).Methods Clinical data of the patient was analyzed.Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA.Next-generation sequencing(NGS)was then carried out.Candidate variants were confirmed by Sanger sequencing.A variety of bioinformatic tools including Mutation Taster,PROVEAN,and PolyPhen2 were used to predict the pathogenicity of the variants based on guidelines from the American College of Medical Genetics and Genomics(ACMG).Results The patient,a 1-month-and-7-day-old male,had presented with cutaneous erythema and fine scaling of the whole body.NGS revealed that he has harbored compound heterozygous variants c.1579G>A(p.Val527Met)(paternal)and c.923T>C(p.Leu308Pro)(maternal)of the ALOX12B gene.The former was known to be likely pathogenic,while the latter was unreported previously and categorized as"likely pathogenic"based on the ACMG guidelines.Based on the clinical and genetic findings,the patient was diagnosed with ARCI.Conclusion The c.1579G>A and c.923T>C variants of the ALOX12B genes probably underlay the ARCI in this patient.Above finding has enriched the spectrum of ALOX12B mutations and enabled molecular diagnosis of the patient,based on which genetic counseling and prenatal diagnosis may be provided.

关 键 词：鱼鳞病 ALOX12B基因 基因变异 

分 类 号：R758.52[医药卫生—皮肤病学与性病学]