Identical <i><scp>COL</scp>71A1</i> heterozygous mutations resulting in different dystrophic epidermolysis bullosa phenotypes

Knöpfel, Nicole; Noguera‐Morel, Lucero; Hernández‐Martín, Ángela; García‐Martín, Adela; García, Marta; Mencía, Ángeles; Pedrero, Rocío Maseda; Lucas, R. de; Escámez, M.J.; Torrelo, Antonio

doi:10.1111/pde.13367

Cited by 3 publications

(2 citation statements)

References 17 publications

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“…The clinical outcome and the inheritance pattern of DEB largely depends on the nature and position of mutations in the COL7A1 gene, especially when glycine substitutions within the triple helix of collagen VII are involved, notably in DDEB. However, a clear genotype-phenotype correlation is still missing in the literature [3,8]. In particular, missense variants at codon 2680 of COL7A1 gene have been described in association with different clinical subtypes of EB.…”

Section: Exome Sequencing In a Consanguineous Pakistani Family Identimentioning

confidence: 99%

Whole-exome sequencing in a consanguineous Pakistani family identifies a mutational hotspot in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosa

Rehman

Peter

Quinodoz

et al. 2020

Clinical Dysmorphology

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Dystrophic epidermolysis bullosa is a major form of epidermolysis bullosa and may be inherited as an autosomal dominant or recessive trait, with associated mutations in the COL7A1 gene. Here, we describe a consanguineous Pakistani family with four affected individuals suffering from recessive dystrophic epidermolysis bullosa. Exome sequencing of the proband’s DNA revealed a homozygous missense variant (c.8038G>A:p.Gly2680Ser) in COL7A1 which cosegregated with disease in the family. The emergence of this particular glycine substitution in patients from diverse ethnic backgrounds such as China, United Kingdom, Poland, Iran, and Pakistan indicates that this variant most likely constitutes a recurrent mutational hotspot in the COL7A1 gene, rather than a germline mutation present at low levels in the general population.

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Section: Exome Sequencing In a Consanguineous Pakistani Family Identimentioning

confidence: 99%

Whole-exome sequencing in a consanguineous Pakistani family identifies a mutational hotspot in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosa

Rehman

Peter

Quinodoz

et al. 2020

Clinical Dysmorphology

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“… 1 , 2 , 3 However, genotype-phenotype correlation is not consistent and identical variants could result in different phenotypes, which suggests that other factors, genetic or environmental, may be involved in this phenotype divergence. 1 , 4 …”

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confidence: 99%

A case of dystrophic epidermolysis bullosa with a rare COL7A1 variant

Amoedo,

Grangeia,

Peralta

et al. 2024

Anais Brasileiros de Dermatologia

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Clinical and allelic heterogeneity in dystrophic epidermolysis bullosa- lessons from an Indian cohort

Gupta,

Jayashankar,

Srinivas

et al. 2023

PLoS ONE

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Background Dystrophic epidermolysis bullosa (DEB) is due to variation in the COL7A1 gene. The clinical phenotype and severity depends on the type of variation and domain of the affected protein. Objectives To characterize the spectrum of COL7A1 variations in a cohort of DEB patients from India, to correlate these findings with clinical phenotypes and to establish a genotype-phenotype correlation. Methods This was a retrospective, observational study involving patients with DEB diagnosed on the basis of clinical manifestations, Immuno-fluorescence antigen mapping (IFM) and genetic analysis. A genotype-phenotype correlation was attempted and observations were further explained using IFM on skin biopsies and molecular dynamic simulations. Descriptive statistics were performed using SPSS version 20.0 with P values of <0.05 considered significant. Results We report 68 unrelated Indian DEB patients classified as RDEB-Intermediate (RDEB-I), RDEB-Severe (RDEB-S) or DDEB based on the EB diagnostic matrix, immunofluorescence antigen mapping and genetic data. Of 68 DEB patients, 59 (86.76%) were inherited in a recessive pattern (RDEB) and 9 (13.24%) in a dominant pattern (DDEB). Limbal stem cell deficiency was seen in four cases of RDEB-S very early in the course of the disease. A total of 88 variants were detected of which 66 were novel. There were no hotspots and recurrent variations were seen in a very small group of patients. We found a high frequency of compound heterozygotes (CH) in RDEB patients born out of non-consanguineous marriage. RDEB patients older than two years who had oral mucosal involvement, and/or deformities, were more likely to have esophageal involvement. Genotype phenotype correlation showed a higher frequency of extracutaneous manifestations and deformities in patients with Premature Termination Codons (PTCs) than in patients with other variations. Molecular simulation studies in patients with missense mutations showed severe phenotype when they were localized in interrupted regions of GLY-X-Y repeats. Conclusion This large study of DEB patients in South Asia adds to the continually expanding genetic database of this condition. This study has direct implications on management as this group of patients can be screened early and managed appropriately.

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Identical COL71A1 heterozygous mutations resulting in different dystrophic epidermolysis bullosa phenotypes

Cited by 3 publications

References 17 publications

Whole-exome sequencing in a consanguineous Pakistani family identifies a mutational hotspot in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosa

Whole-exome sequencing in a consanguineous Pakistani family identifies a mutational hotspot in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosa

A case of dystrophic epidermolysis bullosa with a rare COL7A1 variant

Clinical and allelic heterogeneity in dystrophic epidermolysis bullosa- lessons from an Indian cohort

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