title: Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations.
abstract: Merosin deficient congenital muscular dystrophy 1A (MDC1A) results from mutations in the LAMA2 gene. We report 51 patients with MDC1A and examine the relationship between degree of merosin expression, genotype and clinical features. Thirty-three patients had absence of merosin and 13 showed some residual merosin. Compared to the residual merosin group, patients with absent merosin had an earlier presentation (<7days) (P=0.0073), were more likely to lack independent ambulation (P=0.0215), or require enteral feeding (P=0.0099) and ventilatory support (P=0.0354). We identified 33 novel LAMA2 mutations; these were distributed throughout the gene in patients with absent merosin, with minor clusters in exon 27, 14, 25 and 26 (55% of mutations). Patients with residual merosin often carried at least one splice site mutation and less frequently frameshift mutations. This large study identified novel LAMA2 mutations and highlights the role of immunohistochemical studies for merosin status in predicting clinical severity of MDC1A.
authors.affiliation: Dubowitz Neuromuscular Centre, Institute of Child Health & Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, United Kingdom.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Geranmayeh
authors.forename: Emma
authors.initials: E
authors.lastname: Clement
authors.forename: Lucy H
authors.initials: LH
authors.lastname: Feng
authors.forename: Caroline
authors.initials: C
authors.lastname: Sewry
authors.forename: Judith
authors.initials: J
authors.lastname: Pagan
authors.forename: Rachael
authors.initials: R
authors.lastname: Mein
authors.forename: Stephen
authors.initials: S
authors.lastname: Abbs
authors.forename: Louise
authors.initials: L
authors.lastname: Brueton
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Childs
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
authors.forename: Christian G
authors.initials: CG
authors.lastname: De Goede
authors.forename: Bryan
authors.initials: B
authors.lastname: Lynch
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lin
authors.forename: Gabriel
authors.initials: G
authors.lastname: Chow
authors.forename: Carlos de
authors.initials: Cd
authors.lastname: Sousa
authors.forename: Olivia
authors.initials: O
authors.lastname: O'Mahony
authors.forename: Anirban
authors.initials: A
authors.lastname: Majumdar
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Katherine
authors.initials: K
authors.lastname: Bushby
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D051346:Mobility Limitation; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics; D012133:Respiratory Paralysis; D055815:Young Adult
chemical_list: D007797:Laminin; D022821:RNA Splice Sites; C102645:laminin alpha 2