title: Charcot-Marie-Tooth 4B2 caused by a novel mutation in the MTMR13/SBF2 gene in two related Portuguese families.
abstract: BACKGROUND
  CMT4B2 is a rare subtype of CMT caused by pathogenic mutations in the myotubularin-related protein-13/set binding factor 2 (MTMR13/SBF2) gene. Nerve conduction velocities are markedly reduced and focally folded myelin sheaths are present on nerve biopsies. We presented two patients from two related Portuguese families with peripheral neuropathy caused by a novel mutation in the MTMR13/SBF2 gene.
  
  
  METHODS
  Family 1: Patient 1: A 30-year-old woman, with disease onset in early childhood presented pes cavus and hammertoes and walked with a steppage gait. Muscle weakness was present distally, myotactic reflexes were abolished and sensory examination revealed a stocking and glove pattern of hypoesthesia to all sensory modalities. Family 2: Patient 2: A 43-year-old man, second degree cousin of patient 1, born of a consanguineous marriage. At the age of 9 months, he was diagnosed with congenital glaucoma on the left eye, with progressive visual loss up to total blindness. He presented bilateral claw hand deformity, pes cavus and hammertoes and walked with a steppage gait. Myotactic reflexes were abolished and muscle weakness was severe distally in the upper and lower limbs. Sensory examination revealed a stocking and glove pattern of hypoesthesia to all modalities. In both patients electrodiagnostic studies evidenced an uniform and generalized sensorimotor demyelinating polyneuropathy and the molecular study found a frameshift/truncating homozygous novel mutation c.5073_5074del (p.Ser1692Tyrfs*42) in the MTMR13/SBF2 gene.
  
  
  CONCLUSIONS
  We report a novel mutation in the MTMR13/SBF2 gene associated with a classical CMT phenotype. Congenital glaucoma associated with a frameshift/truncating mutation in CMT4B2 is reported for the first time.
authors: Unidade de Doenças Neuromusculares, Serviço de Neurologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;
authors: Luís
authors: L
authors: Negrão
authors: Unidade de Doenças Neuromusculares, Serviço de Neurologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;
authors: Luciano
authors: L
authors: Almendra
authors: Unidade de Doenças Neuromusculares, Serviço de Neurologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;
authors: Joana
authors: J
authors: Ribeiro
authors: Unidade de Doenças Neuromusculares, Serviço de Neurologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;
authors: Anabela
authors: A
authors: Matos
authors: Unidade de Doenças Neuromusculares, Serviço de Neurologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;
authors: Argemiro
authors: A
authors: Geraldo
authors: Centro de Genética Clínica, Porto, Portugal.
authors: Jorge
authors: J
authors: Pinto-Basto
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D003241:Consanguinity; D005260:Female; D005901:Glaucoma / Q000151:congenital / Q000209:etiology; D006801:Humans; D008297:Male; D009154:Mutation; D064926:Neurophysiological Monitoring / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000209:etiology*; D011174:Portugal; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*
chemical_list: D054558:Protein Tyrosine Phosphatases, Non-Receptor; C475072:SBF2 protein, human
keywords: CMT4B2; MTMR13/SBF2 gene; autosomal recessive CMT; congenital glaucoma