Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing

Uddin, S. A.; Cesarato, Nicole; Humbatova, Aytaj; Schmidt, Axel; Ur-Rehman, F.; Naeem, Muhammad; Tareen, Abdul Samad; Wolf, Sabrina; Panezai, Muhammad Anwar; Thiele, Holger; Wali, Abdul; Fölster‐Holst, Regina; Basit, Sulman; Ayub, Muhammad; Betz, Regina C.

doi:10.2340/00015555-3634

Cited by 2 publications

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References 34 publications

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“…This disorder comes in two forms based on the pattern of inheritance: autosomal dominant DEB (DDEB; OMIM: 131750) and autosomal recessive DEB (RDEB; OMIM: 226600). The latter form is more severe; RDEB patients typically present with systemic blistering/scarring of the skin and mucous membranes, as well as defects in other organs (2)(3)(4).…”

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confidence: 99%

Genetic analysis and prenatal diagnosis of recessive dystrophic epidermolysis bullosa caused by compound heterozygous variants of the COL7A1 gene in a Chinese family

et al. 2022

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BackgroundDystrophic epidermolysis bullosa (DEB) is an incurable and inherited skin disorder mainly caused by mutations in the gene encoding type VII collagen (COL7A1). The purpose of this study was to identify the causative genetic variants and further perform genetic diagnosis in a Chinese family affected by DEB.MethodsHigh-throughput sequencing was performed to analyze the genetic skin disorder-related genes of parents of the proband, and the variants were further confirmed in the other members by Sanger sequencing. Sanger sequencing, karyotype analysis, and chromosomal microarray analysis (CMA) were used together for prenatal diagnosis after the second pregnancy. The phenotype of the fetus was tracked after the diagnosis and induction of labor. Moreover, skin and muscle pathological examination and whole-exome sequencing (WES) of the skin and muscle tissue of the induced fetus were performed.ResultsHere, we determined two heterozygous variants of the COL7A1 gene that contributed to the autosomal recessive DEB (RDEB) in the family, i.e., a novel pathogenic variant (c.8335G > T, p.E2779*) and a likely pathogenic variant (c.7957G > A, p.G2653R). Sanger sequencing of amniotic fluid cells showed that the fetus carried the above two compound heterozygous variants, and the karyotype analysis and CMA results showed no abnormality. The clinical phenotype and pathological results of the induced fetus were consistent with the characteristics of DEB. Further, WES analysis also confirmed a novel compound heterozygous variation in COL7A1, consisting of two variants, namely, c.8335G > T and c.7957G > A in the fetus.ConclusionThis study expands the spectrum of disease-causing variants of COL7A1 and provides a theoretical basis for diagnosis, genetic counseling, and prognosis of families affected by RDEB

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Section: Introductionmentioning

confidence: 99%

Genetic analysis and prenatal diagnosis of recessive dystrophic epidermolysis bullosa caused by compound heterozygous variants of the COL7A1 gene in a Chinese family

et al. 2022

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Dystrophic epidermolysis bullosa: genotype-phenotype correlations

Kubanov,

Chikin,

Karamova

2023

Vestnik dermatologii i venerologii

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Dystrophic epidermolysis bullosa is caused by mutations in the COL7A1 gene. The disease characterized by clinical heterogeneity. To date, scientific findings allow to evaluate correlations between the severity of clinical manifestations and genetic defects underlying in the development of the disease. A systematic literature search was performed using PubMed and RSCI, and keywords including dystrophic epidermolysis bullosa, collagen VII, COL7A1. The review includes description of clinical findings of dystrophic epidermolysis bullosa. The types and localization of pathogenic mutations of the COL7A1 gene, their influence on the protein synthesis, structure and functioning are characterized. The correlation between severe course of dystrophic epidermolysis bullosa and mutations resulting in premature termination codons generation which associate with the absence of type VII collagen at the dermo-epidermal junction has been described. Nevertheless, genotype-phenotype correlations should be analyzed carefully due to mechanisms which enable to restore protein expression as well as the possibility of the formation of premature termination codons associated with a more severe course of the disease, when replacing nucleotides in case of their influence on splicing. Keywords: dystrophic epidermolysis bullosa; COL7A1, collagen VII, hinge region, glycine substitutions

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Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing

Cited by 2 publications

References 34 publications

Genetic analysis and prenatal diagnosis of recessive dystrophic epidermolysis bullosa caused by compound heterozygous variants of the COL7A1 gene in a Chinese family

Genetic analysis and prenatal diagnosis of recessive dystrophic epidermolysis bullosa caused by compound heterozygous variants of the COL7A1 gene in a Chinese family

Dystrophic epidermolysis bullosa: genotype-phenotype correlations

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