Novel biallelic variants in COL7A1 cause recessive dystrophic epidermolysis bullosa

Abstract

Background Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is an incurable and severe inherited skin disorder characterized by recurrent blistering at the sublamina densa beneath the cutaneous basement membrane. It is caused by biallelic loss‐of‐function mutation in the gene encoding type VII collagen ( COL7A1 ). This study aimed to identify the causative variants of a Chinese RDEB patient and further provide prenatal diagnosis for the ongoing risk pregnancy of the proband's mother. Methods Clinical exome sequencing (CES) has been performed and an in‐house pipeline was used to conduct a phenotype‐driven data analysis. A minigene assay was used to verify the pathogenicity of a novel splice site variant in the COL7A1 . Results Here we report two compound heterozygous variants in COL7A1 , c.3867delT (p.G1290Efs*35) and c.5532+4_5532+5delAG, identified in a RDEB patient by CES. The minigene assay confirmed that thec.5532+4_5532+5delAGchange was a noncanonic splice site variant leading to in an in‐frame deletion of exon 64. Prenatal diagnosis indicated that the present pregnancy of the patient's mother was not affected. Conclusion Our study expands the mutation spectrum of COL7A1 and demonstrated that CES and minigene assays were efficient tools for RDEB molecular diagnoses.

Multiple genetic variants involved in both autoimmunity and autoinflammation detected in Chinese patients with sporadic Meniere's disease: a preliminary study

“…Mutations in MEFV have been defined as variants specific to autoinflammatory diseases and have also been detected in autoimmune diseases ( 26 , 27 ). Mutations in COL7A1 , which encodes type VII collagen, have been reported to cause dystrophic epidermolysis bullosa, an inherited epidermolysis bullosa that demonstrates activated autoimmunity and inflammatory responses ( 28 ). Mutations in COL7A1 were reported to potentially overlap with the TMIE gene that is involved in the mechanoelectrical transduction of cochlear hair cells and detected in a case of bilateral auditory neuropathy ( 29 ).…”

Epidermolysis Bullosa and Rickets in a 21-Year-Old Female: A Case Report

“…COL7A1 contains 118 exons that encode the alpha-1 chain of collagen type VII, which consists of 2,944 amino acids. This collagen functions as an anchor between the epithelial tissue and the stroma underneath [ 10 ].…”

Abordagem odontológica em crianças e adolescentes com epidermólise bolhosa - revisão integrativa / Dental approach in children and adolescents with epidermolysis bullosa – integrative review

“…Por outro lado, embora lesões de cárie sejam frequentemente relatadas em pacientes com EB, não existe consenso demonstrando essa relação de causalidade. É plausível justificar uma alta incidência de lesões de cárie pela dificuldade de higienização bucal própria desses pacientes e o excessivo consumo de alimentos pastosos e ricos em sacarose (YANG et al, 2020;VENTI et al, 2019;TORRES et al, 2011;PFENDNER;LUCKY, 2018;MELLO et al, 2016;KUMMER et al, 2013;KRISHNA;PARMAR;HAS, 2014;HANDA et al, 2016;GALEOTTI et al, 2014;ESWARA, 2012;ESFAHANIZADE et al, 2014;DIOCIAIUTI et al, 2013;DAG;BEZGIN;ÖZALP, 2014;CHUANG;HSU;LIS 2015;ARGYROPOULOU et al, 2018;AL-ABADI et al, 2016).…”

“…Relato de casoRelatar caso clínico com evidências de uma alternativa simples, segura, estética e econômica para a reabilitação protética de pacientes com EB. Todas as etapas preliminares e operatórias são descritas para o uso de placas termolaminadas a vácuo como base estrutural para uma prótese removível para um paciente com EBYang et al, 2020 Relato de caso Este estudo teve como objetivo identificar as variantes causais de uma paciente chinesa RDEB e ainda fornecer o diagnóstico pré-natal para a gravidez de risco em curso da mãe do probando.…”