title: Novel mutations in LAMA2 gene responsible for a severe phenotype of congenital muscular dystrophy in two Tunisian families.
abstract: Congenital muscular dystrophies are a group of common genetically determined disorders often transmitted with a recessive mode of inheritance. In recent years, several deficiencies of proteins from the muscle membrane, extra cellular matrix, sarcomere, muscle cytosol and the nucleus have been described to cause CMD. The occidental type of CMD (MDC1A) in which the primary defect is a deficiency in laminin alpha2 chain (merosin) encoded by LAMA2 gene, accounts for 30-40% of cases. The clinical course of CMD with complete laminin alpha2 chain deficiency may be variable but most often; severe forms characterized by hypotonia at birth, profound muscle weakness, marked delay in motor milestones are observed. Since the identification of the first LAMA2 gene mutations leading to merosin deficiency in 1995, several mutations have subsequently been reported in many exons of this gene without any "hotspot" region. In this work, we report two novel homozygous mutations c.8005delT and c.8244+1G>A in the LAMA2 gene in four Tunisian patients with a severe MDC1A phenotype belonging to two unrelated consanguineous families.
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, 3029 Sfax, Tunisie. nacim.louhichi@fss.rnu.tn
authors.forename: N
authors.initials: N
authors.lastname: Louhichi
authors.forename: P
authors.initials: P
authors.lastname: Richard
authors.forename: C H
authors.initials: CH
authors.lastname: Triki
authors.forename: M
authors.initials: M
authors.lastname: Meziou
authors.forename: H
authors.initials: H
authors.lastname: Ayadi
authors.forename: P
authors.initials: P
authors.lastname: Guicheney
authors.forename: F
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005808:Genes, Recessive / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015151:Immunoblotting; D007797:Laminin / Q000172:deficiency / Q000235:genetics*; D009136:Muscular Dystrophies / Q000151:congenital / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D014416:Tunisia / Q000453:epidemiology
chemical_list: D007797:Laminin; C102645:laminin alpha 2