A founder deletion in ECM1 of 1163 bp causes lipoid proteinosis in the southeast region of Turkiye

Abstract

AbstractLipoid proteinosis (LP) is an inherited disorder characterized by the accumulation of hyaline‐like material in the skin, oral cavity, and larynx. The primary symptoms include hoarseness, restricted tongue movements, and various skin lesions. LP is caused by biallelic pathogenic variants in the ECM1 gene. We studied 20 patients from nine different families with LP, 19 of whom are from Şanlıurfa in the southeastern region of Turkiye. Overall, the clinical features of the patient cohort were consistent with those mentioned in the literature, except for one exhibited an atrophoderma vermiculatum‐like lesion, which is atypical for LP. The clinical exome sequencing analysis revealed three different homozygous variants in the ECM1 gene (NM_004425). While c.1246C>T p.(Arg416*) on Exon 8 and c.806G>A p.(Cys269Tyr) on Exon 7 were detected in 1 patient each, an intragenic deletion of 1163 base‐pairs including Exons 9 and 10 (c.1304 + 33_*300del) was identified in 18 patients from 7 unrelated families. The haplotype analysis of the deletion variant indicated a founder effect in the families from the Şanlıurfa province of Turkiye. Based on all this information, copy number variation analysis is recommended for patients with LP. In addition to this rare observation, this study represents the largest examination of the molecular spectrum of LP patients in Turkiye, alongside the clinical spectrum.