Congenital lamellar ichthyosis in Tunisia is caused by a founder nonsense mutation in the TGM1 gene

Abstract

Lamellar ichthyosis (LI, MIM# 242300) is a severe autosomal recessive genodermatosis present at birth in the form of collodion membrane covering the neonate. Mutations in the TGM1 gene encoding transglutaminase-1 are a major cause of LI. In this study molecular analysis of two LI Tunisian patients revealed a common nonsense c.788G>A mutation in TGM1 gene. The identification of a cluster of LI pedigrees carrying the c.788G>A mutation in a specific area raises the question of the origin of this mutation from a common ancestor. We carried out a haplotype-based analysis by way of genotyping 4 microsatellite markers and 8 SNPs flanking and within the TGM1 gene spanning a region of 6 Mb. Haplotype reconstruction from genotypes of all members of the affected pedigrees indicated that all carriers for the mutation c.788G>A harbored the same haplotype, indicating common ancestor. The finding of a founder effect in a rare disease is essential for the genetic diagnosis and the genetic counselling of affected LI pedigrees in Tunisia.

Congenital lamellar ichthyosis in Tunisia associated with vitamin D rickets caused by a founder nonsense mutation in the TGM1 gene

“…Hence, children with ichthyosis may require lifelong prophylaxis of calcium and vitamin D . In our patient, a nonsense mutation, the c.788G>A, p.W263X in the TGM1 gene was identified, which is a founder nonsense mutation . The latter was reported in association with lamellar ichthyosis, erythrodermic congenital ichthyosis, and even bathing suit ichthyosis.…”

Mutations of transglutaminase-1 in Chinese patients with autosomal recessive congenital ichthyosis: a case report with clinical and genetic analysis of Chinese cases reported in literature

“…Some researchers have recently confirmed that five different TGM1 mutations are common in some specific ethnic populations. These studies used haplotype‐based analysis with polymorphic microsatellite markers: c.1223_1227delACACA in Portuguese and Galician (NW Spain) patients, c.2278C>T and c.984+1G>A in Galician patients, c.788G>A in Tunisian patients, and c.877‐and 2A>G in Italian, North American and Norwegian patients . This evidently low genetic heterogeneity raises the possibility of founder effects.…”

Novel transglutaminase 1 mutations in a Chinese patient with severe lamellar ichthyosis phenotype

“…[1] Lamellar ichthyosis is a rare, autosomal recessive skin disorder characterized by generalized hyperkeratosis, with estimated incidence rates of 1:250000. [1] Lamellar ichthyosis is a rare, autosomal recessive skin disorder characterized by generalized hyperkeratosis, with estimated incidence rates of 1:250000.…”

“…[1] The primary pathogenic event seems to be follicular occlusion in apocrine gland-bearing skin. [1] The primary pathogenic event seems to be follicular occlusion in apocrine gland-bearing skin.…”

“…[1] The primary pathogenic event seems to be follicular occlusion in apocrine gland-bearing skin. [1] We present an 8-year-old Caucasian girl whose lesions commenced at the age of 6 years as painful nodules in the groins, before any signs of puberty. Though it is a common disease in adults (prevalence 4%) and more frequent in females, it is rare before puberty and after menopause.…”