Objective To assess mutations in the ALDH3A2 gene in two patients with Sj(o)gren-Larsson syndrome manifesting primarily as congenital ichthyosis,mental retardation and spastic paraplegia.Methods Two patients,a 2-year-old girl and a 1.5-year-old boy,with Sj(o)gren-Larsson syndrome were included in this study.None of their family members suffered from this disease.Peripheral blood samples were collected from the two patients,their family members (an elder brother and both parents),and 100 unrelated healthy controls.DNA was extracted from the blood samples,and subjected to PCR for the amplification of 10 encoding exons and their flanking sequences of the ALDH3A2 gene followed by DNA sequencing.Results A homozygous missense mutation c.325G ＞ A,which leads to the substitution of glycine by arginine at position 109,was detected in the ALDH3A2 gene of patient 1,whose parents and elder brother were heterozygous carriers of this mutation.The patient 2 carried compound heterozygous mutations,including c.1157A ＞ G (p.Asn386Ser) inherited from his father and c.1294A ＞ T (p.Arg432X) inherited from his mother.None of these mutations was detected in the unrelated healthy controls.Conclusion The homozygous mutation p.Gly109Arg and compound heterozygous mutations p.Asn386Ser and p.Arg432X present in these patients may be associated with clinical phenotypes of Sj(o)grenLarsson syndrome.%目的 检测2例以先天性鱼鳞病、智力发育迟缓及痉挛性截瘫为主要表现的Sj(o)gren-Larsson 综合征患者的ALDH3A2基因突变情况.方法 2例分别为2岁女性及1.5岁男性儿童,家族中均无类似疾病.提取2例患者及其6例相关亲属(每例患儿的父母及哥哥)外周血DNA,采用PCR扩增ALDH3A2基因编码区的全部外显子及其侧翼序列并测序.同时随机抽取100例无关健康人外周血基因组DNA作对照.结果 基因检测发现,例1的ALDH3A2基因发生c.325G＞A纯合突变,导致氨基酸出现p.Gly109Arg改变,其父母及其未受累的兄长为该突变的杂合携带者.例2的ALDH3A2基因发生c.1157A＞G及c.1294A＞T复合杂合突变,导致氨基酸出现p.Asn386Ser及p.Arg432X改变,突变分别来自父母.100例健康对照者均未见相同突变.结论 在2例Sj(o)gren-Larsson综合征患者中检测到ALDH3A2基因的p.Gly109Arg纯合突变及p.Asn386Ser与p.Arg432X复合杂合突变,该基因突变可能与患者临床表型相关.
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