title: Large genomic deletions: a novel cause of Ullrich congenital muscular dystrophy.
abstract: Two mutational mechanisms are known to underlie Ullrich congenital muscular dystrophy (UCMD): heterozygous dominant negatively-acting mutations and recessively-acting loss-of-function mutations. We describe large genomic deletions on chromosome 21q22.3 as a novel type of mutation underlying recessively inherited UCMD in 2 families. Clinically unaffected parents carrying large genomic deletions of COL6A1and COL6A2also provide conclusive evidence that haploinsufficiency for COL6A1and COL6A2is not a disease mechanism for Bethlem myopathy. Our findings have important implications for the genetic evaluation of patients with collagen VI-related myopathies as well as for potential therapeutic interventions for this patient population.
authors.affiliation: Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: A Reghan
authors.initials: AR
authors.lastname: Foley
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Zou
authors.forename: Michele
authors.initials: M
authors.lastname: Yang
authors.forename: Līvija
authors.initials: L
authors.lastname: Medne
authors.forename: Meganne
authors.initials: M
authors.lastname: Leach
authors.forename: Laura K
authors.initials: LK
authors.lastname: Conlin
authors.forename: Nancy
authors.initials: N
authors.lastname: Spinner
authors.forename: Tamim H
authors.initials: TH
authors.lastname: Shaikh
authors.forename: Marni
authors.initials: M
authors.lastname: Falk
authors.forename: Ann M
authors.initials: AM
authors.lastname: Neumeyer
authors.forename: Laurie
authors.initials: L
authors.lastname: Bliss
authors.forename: Brian S
authors.initials: BS
authors.lastname: Tseng
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Winder
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bönnemann
mesh_terms: D002478:Cells, Cultured; D002675:Child, Preschool; D002874:Chromosome Mapping / Q000706:statistics & numerical data; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D024142:Collagen Type VI / Q000235:genetics; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D057895:Haploinsufficiency / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009136:Muscular Dystrophies / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012598:Sclerosis / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: C504344:COL6A2 protein, human; D024142:Collagen Type VI