A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene

Article Article scientifique Article A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene eng 2002 author Ferreiro-girani Ana 744045 author Monnier Nicole author Romero Norma B author Leroy Jean-Paul author Bönnemann Carsten author Haenggeli Charles-Antoine 123252 author Straub Volker author Voss Wolfgang D author Nivoche Yves author Jungbluth Heinz author Lemainque Arnaud author Voit Thomas author Lunardi Joël author Fardeau Michel author Guicheney Pascale 750-759 10.1002/ana.10231 12112081 0364-5134 Multi-minicore disease is an autosomal recessive congenital myopathy characterized by the presence of multiple, short-length core lesions (minicores) in both muscle fiber types. These lesions being nonspecific and the clinical phenotype being heterogeneous, multi-minicore disease boundaries remain unclear. To identify its genetic basis, we performed a genome-wide screening in a consanguineous Algerian family in which three children presented in infancy with moderate weakness predominant in axial muscles, pelvic girdle and hands, joint hyperlaxity (hand involvement phenotype), and multiple minicores. We mapped the disease to chromosome 19q13 in this family and, subsequently, in three additional families showing a similar phenotype, with a maximum LOD score of 5.19 for D19S570. This locus was excluded in 16 other multi-minicore disease families with predominantly axial weakness, scoliosis, and respiratory insufficiency ("classical" phenotype). In the Algerian family, we identified a novel homozygous missense mutation (P3527S) in the ryanodine receptor type 1 gene, a positional candidate gene responsible for the autosomal dominant congenital myopathy central core disease. New muscle biopsies from the three patients at adulthood demonstrated typical central core disease with rods; no cores were found in the healthy parents. This subgroup of families linked to 19q13 represents the first variant of central core disease with genetically proven recessive inheritance and transient presentation as multi-minicore disease. Adolescent Adult Algeria Amino Acid Sequence Animals Biopsy Child Child, Preschool Chromosomes, Human, Pair 19/genetics Female Genes, Recessive/genetics Genetic Linkage Germany Humans Male Molecular Sequence Data Muscle, Skeletal/pathology/physiopathology Mutation Myopathy, Central Core/diagnosis/genetics/physiopathology Pedigree Phenotype Ryanodine Receptor Calcium Release Channel/genetics/metabolism Sequence Alignment Turkey Dewey 618 58 Département de pédiatrie, gynécologie et obstétrique 223 false Annals of neurology 51 6 94d0e4a6-9827-4f04-95bb-308c3f15fdf6 Article (Published version) Restricted 750-759.pdf 2429345 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene	Annals of neurology			2002	723	0

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Ferreiro-girani, Ana