title: A novel homozygous ISPD gene mutation causing phenotype variability in a consanguineous family.
abstract: Within the group of muscular dystrophies, dystroglycanopathies represent an important subgroup of recessively inherited disorders. Their severity varies from the relatively mild forms of adult-onset limb-girdle muscular dystrophy (LGMD), to the severe congenital muscular dystrophies (CMD) with cerebral and ocular involvement. We describe 2 consanguineous children of Pakistani origin, carrying a new homozygous missense mutation c.367G>A (p.Gly123Arg) in the ISPD gene. Mutations in this gene have been recently reported as a common cause of congenital and limb-girdle muscular dystrophy. Patient 1 is an 8-year-old female with an intermediate phenotype between CMD and early LGMD; patient 2 is a 20-month-old male and second cousin of patient 1, showing a CMD phenotype. Cognitive development, brain MRI, eye examination, electrocardiogram and echocardiogram were normal in both patients. To our knowledge, this is the first report on the co-occurrence of both a CMD/early LGMD intermediate phenotype and a CMD within the same family carrying a homozygous ISPD mutation.
authors.affiliation: Developmental Neurology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Baranello
authors.affiliation: Neuromuscular Disease and Immunology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Saredi
authors.affiliation: Neuromuscular Disease and Immunology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Sansanelli
authors.affiliation: Neuromuscular Disease and Immunology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Savadori
authors.affiliation: Neuromuscular Disease and Immunology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Canioni
authors.affiliation: Neuroradiology Units, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Chiapparini
authors.affiliation: Pediatrics Unit, Department of Molecular and Developmental Medicine, University of Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Balestri
authors.affiliation: Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malandrini
authors.affiliation: Developmental Neurology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Arnoldi
authors.affiliation: Developmental Neurology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pantaleoni
authors.affiliation: Neuromuscular Disease and Immunology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.affiliation: Neuromuscular Disease and Immunology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy. Electronic address: mmora@istituto-besta.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Mora
mesh_terms: D002648:Child; D003241:Consanguinity; D049030:Dystroglycans / Q000378:metabolism; D005190:Family; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007797:Laminin / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics*; D020125:Mutation, Missense; D009713:Nucleotidyltransferases / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: D007797:Laminin; C102645:laminin alpha 2; D049030:Dystroglycans; D009713:Nucleotidyltransferases; C573136:CRPPA protein, human
keywords: Alpha-dystroglycan; Congenital muscular dystrophy; Dystroglycanopathies; ISPD; Limb-girdle muscular dystrophy