title: Lipoid proteinosis: phenotypic heterogeneity in Iranian families with c.507delT mutation in ECM1.
abstract: Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by loss-of-function mutations in the ECM1 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 ECM1. 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 ECM1 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 ECM1, reflecting the observed consanguinity in these families. This large cohort revealed extensive phenotypic variability in individuals with the same mutation in ECM1. 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.
authors.affiliation: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Leila
authors.initials: L
authors.lastname: Youssefian
authors.forename: Hassan
authors.initials: H
authors.lastname: Vahidnezhad
authors.forename: Maryam
authors.initials: M
authors.lastname: Daneshpazhooh
authors.forename: Sina
authors.initials: S
authors.lastname: Abdollahzadeh
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Talari
authors.forename: Alireza
authors.initials: A
authors.lastname: Khoshnevisan
authors.forename: Cheyda
authors.initials: C
authors.lastname: Chams-Davatchi
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Mobasher
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: Shahin
authors.initials: S
authors.lastname: Akhondzadeh
authors.forename: Mina
authors.initials: M
authors.lastname: Tabrizi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007492:Iran; D008065:Lipoid Proteinosis of Urbach and Wiethe / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins
keywords: brain calcification; extracellular matrix protein 1; genetic screen; lipoid proteinosis; phenotypic heterogeneity