Homozygous mutation in PTRH2 gene causes progressive sensorineural deafness and peripheral neuropathy

Am J Med Genet A. 2017 Apr;173(4):1051-1055. doi: 10.1002/ajmg.a.38140.


PTRH2 is an evolutionarily highly conserved mitochondrial protein that belongs to a family of peptidyl-tRNA hydrolases. Recently, patients from two consanguineous families with mutations in the PTRH2 gene were reported. Global developmental delay associated with microcephaly, growth retardation, progressive ataxia, distal muscle weakness with ankle contractures, demyelinating sensorimotor neuropathy, and sensorineural hearing loss were present in all patients, while facial dysmorphism with widely spaced eyes, exotropia, thin upper lip, proximally placed thumbs, and deformities of the fingers and toes were present in some individuals. Here, we report a new family with three siblings affected by sensorineural hearing loss and peripheral neuropathy. Autozygosity mapping followed by exome sequencing identified a previously reported homozygous missense mutation in PTRH2 (c.254A>C; p.(Gln85Pro)). Sanger sequencing confirmed that the variant segregated with the phenotype. In contrast to the previously reported patient, the affected siblings had normal intelligence, milder microcephaly, delayed puberty, myopia, and moderate insensitivity to pain. Our findings expand the clinical phenotype and further demonstrate the clinical heterogeneity related to PTRH2 variants.

Keywords: PTRH2 gene; peripheral neuropathy; sensorineural hearing loss.

MeSH terms

  • Adolescent
  • Base Sequence
  • Carboxylic Ester Hydrolases / genetics*
  • Consanguinity
  • Disease Progression
  • Female
  • Gene Expression
  • Genetic Heterogeneity
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / physiopathology
  • Homozygote*
  • Humans
  • Male
  • Mitochondrial Proteins / genetics*
  • Mutation, Missense*
  • Myopia / physiopathology
  • Pain Insensitivity, Congenital / physiopathology
  • Pedigree
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / genetics*
  • Peripheral Nervous System Diseases / physiopathology
  • Phenotype
  • Puberty, Delayed / physiopathology
  • Siblings


  • Mitochondrial Proteins
  • Carboxylic Ester Hydrolases
  • PTH2 protein, human