Open AccessVariants in the <b><i>PNPLA1</i></b> Gene in Families with Autosomal Recessive Congenital Ichthyosis Reveal Clinical Significance
Author(s) -
Farooq Ahmad,
Ishtiaq Ahmed,
Qamre Alam,
Tanveer Ahmad,
Ammara Khan,
Ijaz Ahmad,
Muhammad Bilal,
Amir Hayat,
Amjad Khan,
Ahmed Waqas,
Misbahuddin M Rafeeq,
Ziaullah M Sain,
Muhammad Umair
Publication year - 2021
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000516943
Subject(s) - sanger sequencing , genetics , congenital ichthyosis , missense mutation , biology , ichthyosis , exome sequencing , locus (genetics) , gene , candidate gene , nonsense mutation , dna sequencing , genetic heterogeneity , mutation , phenotype
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>T; p.Arg298*, family A) and a recurrent missense variant (c.102C>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.