title: Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a Colombian family.
abstract: BACKGROUND
  Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease and more than 40 different mutations have been reported. The recessive Q163X mutation has been described in patients of Spanish ancestry, and a founder mutation in South American patients, originating in Spain has been demonstrated.
  
  
  OBJECTIVE
  We describe physical and histological features, and the molecular impact of mutation Q163X in a Colombian family.
  
  
  METHODS
  We report two female patients, daughters of consanguineous parents, with onset of symptoms within the first two years of life, developing severe functional impairment, without evidence of dysmorphic features, hoarseness or diaphragmatic paralysis. Electrophysiology tests showed a sensory and motor neuropathy with axonal pattern. Sequencing of GDAP1 gene was requested and the study identified a homozygous point mutation (c.487 C>T) in exon 4, resulting in a premature stop codon (p.Q163X). This result confirms the diagnosis of Charcot-Marie-Tooth disease, type 4A.
  
  
  RESULTS
  The patients were referred to Physical Medicine and Rehabilitation service, in order to be evaluated for ambulation assistance. They have been followed by Pulmonology service, for pulmonary function assessment and diaphragmatic paralysis evaluation. Genetic counseling was offered. The study of the genealogy of the patient, phenotypic features, and electrophysiological findings must be included as valuable tools in the clinical approach of the patient with Charcot-Marie-Tooth disease, in order to define a causative mutation. In patients of South American origin, the presence of GDAP1 gene mutations should be considered, especially the Q163X mutation, as the cause of CMT4A disease.
authors: School of Medicine. Instituto de Genética, Universidad Nacional de Colombia, Bogota, Colombia.
authors: Angela M
authors: AM
authors: Martin
authors: School of Medicine. Instituto de Genética, Universidad Nacional de Colombia, Bogota, Colombia.
authors: Silvia J
authors: SJ
authors: Maradei
authors: School of Medicine. Instituto de Genética, Universidad Nacional de Colombia, Bogota, Colombia.
authors: Harvy M
authors: HM
authors: Velasco
mesh_terms: D000293:Adolescent; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D002648:Child; D003105:Colombia; D003241:Consanguinity; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D009419:Nerve Tissue Proteins; D010375:Pedigree; D017354:Point Mutation
chemical_list: C118663:GDAP protein; D009419:Nerve Tissue Proteins
keywords: Charcot-Marie-Tooth Disease; Founder effect; axonal neuropathy; genetic counseling; hereditary sensory and motor neuropathy