Identification and association of recurrent ALOXE3 mutation with non-bullous congenital ichthyosiform erythroderma in two ethnically distinct Pakistani families.

TitleIdentification and association of recurrent ALOXE3 mutation with non-bullous congenital ichthyosiform erythroderma in two ethnically distinct Pakistani families.
Publication TypeJournal Article
Year of Publication2019
AuthorsRahman, SBer, Mir, A, Ahmad, N, Haider, SHusnain, Malik, SAkbar, Nasir, M
JournalCongenit Anom (Kyoto)
Volume59
Issue3
Pagination93-98
Date Published2019 May
ISSN1741-4520
Abstract

Non-bullous congenital ichthyosiform erythroderma (NCIE) is characterized by skin scaling with erythema. In this study, two Pakistani families with NCIE are genetically characterized through Whole Exome and Sanger sequencing to identify molecular basis of the disease. We identified a nonsense homozygous c.2026C>T mutation of ALOXE3, causing premature termination of the eLOX3 protein (p.Q676X). In silico studies predicted impaired enzymatic activity of the premature truncated eLOX3, leading to abnormal synthesis of specific hepoxilin derivatives, essential for epidermal barrier formation. It is the first ever study reporting homozygotes of p.Q676X mutation in ethnically distinct two Pakistani families; otherwise, heterozygotes of the said mutation have been reported in South Asian population only. Hence, mutation seems to be region-specific and may be useful for molecular diagnosis of NCIE. Moreover, our findings should help in genetic counseling and career screening.

DOI10.1111/cga.12303
Alternate JournalCongenit Anom (Kyoto)
PubMed ID29935003
PubMed Central IDPMC6309665
Grant ListR01AR068392 / / NIH, USA /
U54 HG006504 / HG / NHGRI NIH HHS / United States
R01 AR068392 / AR / NIAMS NIH HHS / United States
IRSIP 25 BMS 10 / / HEC, Islamabad, Pakistan /
U54 HG006504 / / Yale Centre for Mendelian Genomics, USA /
/ / IBGE, Islamabad, Pakistan /