Analysis of COL7A1 pathogenic variants in a large cohort of dystrophic epidermolysis bullosa patients from Argentina reveals a new genotype–phenotype correlation

Analysis of COL7A1 pathogenic variants in a large cohort of dystrophic epidermolysis bullosa patients from Argentina reveals a new genotype–phenotype correlation

Dystrophic epidermolysis bullosa (DEB) is a clinically heterogeneous heritable skin disorder, characterized by blistering of the skin and mucous membranes following minor trauma. Dominant (DDEB) and recessive (RDEB) forms are caused by pathogenic variants in COL7A1 gene. Argentina's population...

Full description

Saved in:
Bibliographic Details
Published in:American journal of medical genetics. Part A Vol. 188; no. 11; pp. 3153 - 3161
Main Authors: Natale, Mónica Inés, Manzur, Graciela Beatriz, Lusso, Silvina Beatriz, Cella, Eliana, Giovo, María Elsa, Andrada, Romina, Goitia, Juana, Fernández, María Florencia, Della Giovanna, Patricia Silvia, Guillamondegui, María José, Domínguez, Mariángeles, Gutiérrez, Olga, Izquierdo, Agustín, Hernández Herrera, Heliana, Velázquez Perdomo, Luz Graciela, Mistchenko, Alicia Susana, Valinotto, Laura Elena
Format: Journal Article
Language:English
Published: Hoboken, USA John Wiley & Sons, Inc 01-11-2022
Wiley Subscription Services, Inc
Subjects:
Argentina - epidemiology
COL7A1
Collagen (type VII)
Collagen Type VII - genetics
Dystrophic epidermolysis bullosa
Epidermolysis bullosa
Epidermolysis Bullosa Dystrophica - genetics
Gene therapy
Genetic Association Studies
genodermatosis
Genotypes
Geographical distribution
Humans
Mucosa
Mutation
Phenotype
Phenotypes
Population genetics
Population studies
Skin diseases
Trauma
Argentina
COL7A1
genodermatosis
dystrophic epidermolysis bullosa
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Dystrophic epidermolysis bullosa (DEB) is a clinically heterogeneous heritable skin disorder, characterized by blistering of the skin and mucous membranes following minor trauma. Dominant (DDEB) and recessive (RDEB) forms are caused by pathogenic variants in COL7A1 gene. Argentina's population has a heterogeneous genetic background, and little is known about the molecular basis of DEB in our country or in native South American populations. In this study, we present the prevalence and geographical distribution of pathogenic variants found in 181 patients from 136 unrelated families (31 DDEB and 105 RDEB). We detected 95 different variants, 59 of them were previously reported in the literature and 36 were novel, nine of which were detected in more than one family. The most prevalent pathogenic variants were identified in exon 73 in DDEB patients and in exon 3 in RDEB patients. We also report a new phenotype–genotype correlation found in 10 unrelated families presenting mild blistering and severe mucosal involvement. Molecular studies in populations with an unexplored genetic background like ours revealed a diversity of pathogenic variants, and we hope that these findings will contribute to the definition of targets for new gene therapies.
Bibliography:Mónica Inés Natale and Graciela Beatriz Manzur should be considered joint first author.
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.62957