Phenotypical features of two patients diagnosed with PHARC syndrome and carriers of a new homozygous mutation in the ABHD12 gene

Autores de IIS La Fe

• Marina Frasquet Carrera

  Autor

• Vincenzo Lupo

  Autor

• Maria Jose Chumillas Lujan

  Autor

• Juan Francisco Vázquez Costa

  Autor

• Carmen Espinos Armero

  Autor

• 

  Teresa Sevilla Mantecón

  Autor

Grupos

• Patología Neuromuscular y Ataxias

  

  Investigador Principal

  Teresa Sevilla Mantecón

Abstract

PHARC (Polyneuropathy, Hearing loss, Ataxia, Retinitis pigmentosa and Cataracts) (MIM# 612674) is an autosomal recessive neurodegenerative disease caused by mutations in the ABHD12 gene. We evaluated two Spanish siblings affected with pes cavus, sensorimotor neuropathy, hearing loss, retinitis pigmentosa and juvenile cataracts in whom the genetic test of ABHD12 revealed a novel homozygous frameshift mutation, c.211_223de1 (p.Arg71Tyrfs*26). The earliest clinical manifestation in these patients was a demyelinating neuropathy manifested with a Charcot-Marie-Tooth phenotype over three decades. Progressive hearing loss, cataracts and retinitis pigmentosa appeared after the age of 30. We herein describe the complete clinical picture of these two patients, and focus particularly on neuropathy characteristics. This study supports the fact that although PHARC is rare, its phenotype is very characteristic and we should include its study in patients affected with demyelinating polyneuropathy, hearing loss and retinopathy.

Keywords

• Charcot-Marie-Tooth disease; ARLID12 gene; PHARC; Deaf-blindness; Usher syndrome