title: Exome sequencing identifies Laing distal myopathy MYH7 mutation in a Roma family previously diagnosed with distal neuronopathy.
abstract: We describe a Hungarian Roma family, originally investigated for autosomal dominant distal muscular atrophy. The mother started toe walking at 3 years and lost ambulation at age 27. Her three daughters presented with early steppage gait and showed variable progression. Muscle biopsies were nonspecific showing myogenic lesions in the mother and lesions resembling neurogenic atrophy in the two siblings. To identify the causative abnormality whole exome sequencing was performed in two affected girls and their unaffected father, unexpectedly revealing the MYH7 mutation c.4849_4851delAAG (p.K1617del) in both girls, reported to be causative for Laing distal myopathy. Sanger sequencing confirmed the mutation in the affected mother and third affected daughter. In line with variable severity in Laing distal myopathy our patients presented a more severe phenotype. Our case is the first demonstration of Laing distal myopathy in the Roma and the successful use of whole exome sequencing in obtaining a definitive diagnosis in ambiguous cases.
authors.affiliation: Department of Medical Genetics, Szentágothai Research Center, University of Pécs, Pécs, Hungary. Electronic address: komlosi.katalin@pte.hu.
authors.forename: Katalin
authors.initials: K
authors.lastname: Komlósi
authors.affiliation: Department of Medical Genetics, Szentágothai Research Center, University of Pécs, Pécs, Hungary.
authors.forename: Kinga
authors.initials: K
authors.lastname: Hadzsiev
authors.affiliation: Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany; Institute for Genetics, University of Cologne, 50674 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Garbes
authors.affiliation: Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany; Institute for Genetics, University of Cologne, 50674 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Lilian A
authors.initials: LA
authors.lastname: Martínez Carrera
authors.affiliation: Neurology Clinic, University of Pécs, Pécs, Hungary.
authors.forename: Endre
authors.initials: E
authors.lastname: Pál
authors.affiliation: deCODE Genetics, Reykjavik, Iceland.
authors.forename: Jóhann Haukur
authors.initials: JH
authors.lastname: Sigurðsson
authors.affiliation: deCODE Genetics, Reykjavik, Iceland.
authors.forename: Olafur
authors.initials: O
authors.lastname: Magnusson
authors.affiliation: Department of Medical Genetics, Szentágothai Research Center, University of Pécs, Pécs, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
authors.affiliation: Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany; Institute for Genetics, University of Cologne, 50674 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Wirth
mesh_terms: D000328:Adult; D001483:Base Sequence; D024722:Cardiac Myosins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D049310:Distal Myopathies / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D059472:Exome; D005190:Family; D005260:Female; D006801:Humans; D006814:Hungary; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index
chemical_list: C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains
keywords: Distal myopathy; Laing distal myopathy; MYH7; Myosinopathies; Whole exome sequencing