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Lipoid proteinosis: phenotypic heterogeneity in Iranian families with c.507delT mutation in ECM 1
Author(s) -
Youssefian Leila,
Vahidnezhad Hassan,
Daneshpazhooh Maryam,
Abdollahzadeh Sina,
Talari Hamidreza,
Khoshnevisan Alireza,
ChamsDavatchi Cheyda,
Mobasher Roozbeh,
Li Qiaoli,
Uitto Jouni,
Akhondzadeh Shahin,
Tabrizi Mina
Publication year - 2015
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12620
Subject(s) - sanger sequencing , genetic heterogeneity , phenotype , mutation , genetics , medicine , nonsense mutation , exon , exome sequencing , biology , pathology , missense mutation , gene
Lipoid proteinosis ( LP ) is a rare autosomal recessive genodermatosis caused by loss‐of‐function mutations in the ECM 1 gene, and previous studies have noted phenotypic variability. In this study, we examined 12 patients representing three Iranian families for clinical manifestations and genotyped them for mutations in ECM 1 . LP was diagnosed with characteristic mucocutaneous and neurologic manifestations. Five patients were also subjected to magnetic resonance imaging ( MRI )/computed tomography ( CT ) scan of the central nervous system. DNA was isolated from peripheral blood from patients and their clinically unaffected relatives, and mutations in ECM 1 were sought by PCR ‐based amplification of all exons and flanking intronic sequences, followed by bidirectional Sanger sequencing. Significant phenotypic variability in this multisystem disorder, including presence of convulsions and epilepsy in about half of the patients was noted. In most cases, this was associated with calcifications in the brain detected by MRI / CT scans. Genotyping of the affected individuals in three families from the central region of Iran revealed presence of homozygous c.507delT mutation in ECM 1 , reflecting the observed consanguinity in these families. This large cohort revealed extensive phenotypic variability in individuals with the same mutation in ECM 1 . This observation suggests a role for genetic and epigenetic as well as environmental modulation of the phenotype. Identification of mutations allows screening of unaffected individuals for presence or absence of this mutation in extended LP families, with implications for genetic counseling.