title: Clinical, neurophysiological and morphological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy.
abstract: Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) was associated with mutations in the YARS gene, encoding tyrosyl-tRNA synthetase, in two large unrelated Bulgarian and US pedigrees and one sporadic case. Here for the first time we describe the clinical, neurophysiological and histopathological features, and phenotypic differences between these two DI-CMTC families. Twenty-one affected individuals from the US family and 27 from the Bulgarian family were evaluated. The mean age of onset in US subjects was 10.7 years in men and 7.3 years in women, while in the Bulgarian participants it was 18.2 years in men and 33.7 years in women. The course was slowly progressive. Extensor digitorum brevis atrophy was uniform. Atrophy and/or weakness of upper and lower limb muscles were found in over 50 % of the subjects. Nerve conduction studies (NCS) were abnormal in all US adults and five of six children and all Bulgarian patients except one asymptomatic 25-year-old man. Median motor NCS were in the range of 29.5-45.6 m/s in the US family and 24.7-57.8 m/s in the Bulgarian family. Sural sensory nerve action potentials were absent in 14/21 and 4/12 NCS from adult US and Bulgarian participants, respectively. Analysis of sural nerve biopsies from US patients revealed age-dependent morphological changes of axonal degeneration, absence of onion bulbs, and <10 % fibers with segmental remyelination. Our findings provide further insights into the diagnosis and pathology of intermediate CMT. They also extend the phenotypic spectrum of peripheral neuropathies associated with aminoacyl-tRNA synthetase mutations.
authors.affiliation: Department of Neurology, St. Louis University School of Medicine, 1438 South Grand Boulevard, St. Louis, MO, 63104, USA. thomasfp@slu.edu.|Department of Physical Therapy and Athletic Training, Institute for Molecular Virology, St. Louis University, St. Louis, MO, USA. thomasfp@slu.edu.
authors.forename: Florian P
authors.initials: FP
authors.lastname: Thomas
authors.affiliation: Department of Neurology, Medical University - Sofia, Sofia, Bulgaria.|Current affiliation: Clinic of Neurology, University Hospital Sofiamed, Sofia, Bulgaria.
authors.forename: Velina
authors.initials: V
authors.lastname: Guergueltcheva
authors.affiliation: Neurology Division, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Francisco A A
authors.initials: FA
authors.lastname: Gondim
authors.affiliation: Department of Neurology, Medical University - Sofia, Sofia, Bulgaria.|Department of Cognitive Science and Psychology, New Bulgarian University, Sofia, Bulgaria.
authors.forename: Ivailo
authors.initials: I
authors.lastname: Tournev
authors.affiliation: Department of Neurology, University Medical Center of Princeton, Princeton, NJ, USA.
authors.forename: Chitharanjan V
authors.initials: CV
authors.lastname: Rao
authors.affiliation: Department of Neurology, Medical University - Sofia, Sofia, Bulgaria.
authors.forename: Boryana
authors.initials: B
authors.lastname: Ishpekova
authors.affiliation: Department of Neurology, St. Louis University School of Medicine, 1438 South Grand Boulevard, St. Louis, MO, 63104, USA.
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Kinsella
authors.affiliation: Department of Neurology, St. Louis University School of Medicine, 1438 South Grand Boulevard, St. Louis, MO, 63104, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Neurology, St. Louis University School of Medicine, 1438 South Grand Boulevard, St. Louis, MO, 63104, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Geller
authors.affiliation: Department of Pediatrics, Medical University-Sofia, Sofia, Bulgaria.
authors.forename: Ivan
authors.initials: I
authors.lastname: Litvinenko
authors.affiliation: Division of Neurology, University Hospital Antwerpen (UZA), Antwerp, Belgium.|Neurogenetics Group, Department of Molecular Genetics, VIB, University of Antwerp, Antwerp, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
authors.affiliation: Molecular Neurogenomics Group, Department of Molecular Genetics, VIB, University of Antwerp, Universiteitsplein 1, Antwerp, Belgium. albena.jordanova@molgen.vib-ua.be.|Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria. albena.jordanova@molgen.vib-ua.be.
authors.forename: Albena
authors.initials: A
authors.lastname: Jordanova
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000328:Adult; D000367:Age Factors; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D004576:Electromyography; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology*; D009460:Neurologic Examination; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology*
keywords: Aminoacyl-tRNA synthetase; Charcot-Marie-tooth disease; Clinical neurology; Intermediate conduction velocities