遗传性鱼鳞病ALOX12B基因的新型致病位点:1例火棉胶样女婴的家系分析

A novel mutation in the ALOX12B gene in hereditary ichthyosis:pedigree analysis for a female collodion baby

目的探讨一家庭连续3胎火棉胶样婴儿的突变基因及遗传方式。方法先证者因出生时周身广泛皮肤干燥、皲裂的表现被诊断为火棉胶样婴儿。父母表型正常,其第1、2胎出生后均存在皮肤干燥、皲裂,且在出生后数日死亡。提取患儿及其父母外周血DNA,进行全基因组外显子捕获测序,并用Sanger测序验证。结果患儿携带ALOX12B基因复合杂合突变:错义突变c.1405 C>T(p.R469W)和移码突变c.68_69ins C(p.L24fs),分别遗传自其父母。结论患儿诊断为遗传性鱼鳞病,为常染色体隐性遗传。ALOX12B基因错义突变c.1405 C>T和移码突变c.68_69ins C可能为引起该患儿临床表型的病因,该移码突变目前国内外尚无报道。

Objective To investigate pathogenic genes and inheritance patterns in 3 consecutive collodion babies in a family.Methods The proband was diagnosed as a collodion baby due to extensive dry and chapped skin all over the body at birth.Phenotypes of the proband's parents were normal,but their first and second children presented with dry and chapped skin at birth and died a few days after birth.DNA was extracted from peripheral blood samples of the patient and her parents for whole-exome capture sequencing,and candidate mutations were verified by Sanger sequencing.Results Compound heterozygous mutations in the ALOX12B gene were identified in the infant,including a missense mutation c.1405 C>T(p.R469w)inherited from her father and a frameshift mutation c.68_69insC(p.L24fs)inherited from her mother.Conclusions The infant was diagnosed with hereditary ichthyosis,which was inherited in an autosomal recessive manner.The missense mutation c.1405 C>T and frameshift mutation c.68_69insC in the ALOX12B gene may contribute to the clinical phenotype of this infant,and the frameshift mutation had not been reported in China or other countries.