title: LAMA2 gene analysis in a cohort of 26 congenital muscular dystrophy patients.
abstract: Congenital muscular dystrophy type 1A (MDC1A) is caused by mutations in the LAMA2 gene encoding laminin-alpha2. We describe the molecular study of 26 patients with clinical presentation, magnetic resonance imaging and/or laminin-alpha2 expression in muscle, compatible with MDC1A. The combination of full genomic sequencing and complementary DNA analysis led to the particularly high mutation detection rate of 96% (50/52 disease alleles). Besides 22 undocumented polymorphisms, 18 different mutations were identified in the course of this work, 14 of which were novel. In particular, we describe the first fully characterized gross deletion in the LAMA2 gene, encompassing exon 56 (c.7750-1713_7899-2153del), detected in 31% of the patients. The only two missense mutations detected were found in heterozygosity with nonsense or truncating mutations in the two patients with the milder clinical presentation and a partial reduction in muscle laminin-alpha2. Our results corroborate the previous few genotype/phenotype correlations in MDC1A and illustrate the importance of screening for gross rearrangements in the LAMA2 gene, which may be underestimated in the literature.
authors.affiliation: Unidade de Genética Molecular, Centro de Genética Médica Dr Jacinto Magalhães, INSARJ, Porto, Portugal. jorge.oliveira@igm.min-saude.pt
authors.forename: J
authors.initials: J
authors.lastname: Oliveira
authors.forename: R
authors.initials: R
authors.lastname: Santos
authors.forename: I
authors.initials: I
authors.lastname: Soares-Silva
authors.forename: P
authors.initials: P
authors.lastname: Jorge
authors.forename: E
authors.initials: E
authors.lastname: Vieira
authors.forename: M E
authors.initials: ME
authors.lastname: Oliveira
authors.forename: A
authors.initials: A
authors.lastname: Moreira
authors.forename: T
authors.initials: T
authors.lastname: Coelho
authors.forename: J C
authors.initials: JC
authors.lastname: Ferreira
authors.forename: M J
authors.initials: MJ
authors.lastname: Fonseca
authors.forename: C
authors.initials: C
authors.lastname: Barbosa
authors.forename: J
authors.initials: J
authors.lastname: Prats
authors.forename: M L
authors.initials: ML
authors.lastname: Aríztegui
authors.forename: M L
authors.initials: ML
authors.lastname: Martins
authors.forename: T
authors.initials: T
authors.lastname: Moreno
authors.forename: K
authors.initials: K
authors.lastname: Heinimann
authors.forename: C
authors.initials: C
authors.lastname: Barbot
authors.forename: S I
authors.initials: SI
authors.lastname: Pascual-Pascual
authors.forename: A
authors.initials: A
authors.lastname: Cabral
authors.forename: I
authors.initials: I
authors.lastname: Fineza
authors.forename: M
authors.initials: M
authors.lastname: Santos
authors.forename: E
authors.initials: E
authors.lastname: Bronze-da-Rocha
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007797:Laminin / Q000235:genetics*; D008297:Male; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D007797:Laminin; C102645:laminin alpha 2