The term autosomal recessive congenital ichthyosis (ARCI) is the subgroup of ichthyosis, which describes a highly heterogeneous group of genetic disorders of the skin characterized by cornification and defective keratinocytes differentiation associated with mutations in at least 14 genes including PNPLA1. To study the molecular basis of the Pakistani kindreds (A and B) affected by ARCI, whole-exome sequencing (WES) in the DNA samples of affected members was performed followed by Sanger sequencing of the candidate gene to hunt down the disease-causing sequence variant/s. WES data analysis led to the identification of a novel nonsense sequence variant (c.892C#x3e;T; p.Arg298*, family A) and a recurrent missense variant (c.102C#x3e;A; p.Asp34Glu, family B) in PNPLA1 mapped to the ARCI locus in chromosome 6p21.31. Validation and cosegregation analysis of the variants in the remaining family members of the respective families were confirmed by Sanger sequencing. The current investigation expands the spectrum of PNPLA1 mutations and helps establish the proper clinico-genetic diagnosis and correct genotype-phenotype correlation.
Mol Syndromol

中文翻译：

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常染色体隐性先天性鱼鳞病家族中的 PNPLA1 基因变异揭示临床意义

常染色体隐性遗传先天性鱼鳞病 (ARCI) 是鱼鳞病的一个亚组，它描述了一组高度异质的皮肤遗传疾病，其特征是与至少 14 个基因（包括PNPLA1 ）的突变相关的角化和有缺陷的角质形成细胞分化。为了研究受ARCI影响的巴基斯坦亲属（A和B）的分子基础，对受影响成员的DNA样本进行全外显子组测序（WES），然后对候选基因进行Sanger测序以寻找致病序列变体/秒。WES 数据分析导致鉴定出一种新的无义序列变体（c.892C#x3e；T；p.Arg298*，家族 A）和反复出现的错义变异（c.102C#x3e；A；p.Asp34Glu，家族 B） ) 在PNPLA1映射到染色体 6p21.31 中的 ARCI 基因座。Sanger测序证实了各个家族剩余家族成员中变体的验证和共分离分析。目前的研究扩大了PNPLA1突变的范围，有助于建立正确的临床-遗传学诊断和正确的基因型-表型相关性。
摩尔综合症