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 PCRbased 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.

Nicotinamide Enhances Repair of Arsenic and Ultraviolet Radiation-Induced DNA Damage in HaCaT Keratinocytes and Ex Vivo Human Skin

“…Our current immunohistochemistry findings are also consistent with our previous photolesion repair curves in keratinocytes using Comet assays [ 18 ]. The observed levels of 8oxoG in unirradiated cells are also consistent with previous studies [ 18 , 29 ], and likely reflect oxidative DNA damage from background ROS production in living cells subjected to cell processing during experimental procedures.…”

Determination of the Carnitine and Acylcarnitine Profile in Patients with Lipoid Proteinosis

“…G. Finocchiaro et al demonstrated that there was a relationship between carnitine palmitoiltransferase (CPTase) activity and chromosome 1q12. More than 52 mutations have been identified in LP together with ECM1 that encodes extracellular matrix protein in chromosome 1q12 [2,18]. In histological studies, the disease is characterised by resistance to diastase in the dermoepidermal component, thickening of the basal membrane and accumulation of hyalin material in blood vessels and adnexial epithelium in addition to the dermis.…”

“…Various skin symptoms emerge in childhood such as papillary, acneform scars at the eyelash roots and wart-like papillae and plaque. A wide clinical heterogenity may be seen even within a family or an isolated patient population [2]. In a 2002 study using genome link analysis, pathogen mutations of ECM1 gene with an accompanying location on chromosome 1q21 were identified in LP [3].…”

“…Since that time a total of 52 different pathogen mutations have been reported, including missense, small and large delesions and insertions. Approximately 50% of the mutations have been shown to be in exons 6 and 7 [2].…”

Lipoid proteinosis: towards predictive clinical clues

“…However, a wide range of clinical heterogeneity may occur among patients with LP, even within a family or an isolated patient population . Youssefian et al . conducted mutation analysis of the ECM1 gene in 12 patients from 3 Iranian family pedigrees, one of which consisted of 5 generations.…”