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

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

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The Triangle Regional Research and Development Center, Kfar Qari', Israel.
Beit-Berl Academic College, Beit-Berl, Israel.
Genetic Institute, Emek Medical Center, Afula, Israel.
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Faculty of Life Sciences, Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv, Israel.
Sakler Faculty of Medicine, Child neurology Unit Mier Medical Cener, Tel-Aviv University, Tel-Aviv, Israel.
Manchester Centre for Genomic Medicine, Manchester Academic Health Sciences Centre, St. Mary's Hospital, Manchester, UK.
Institute of Human Development, Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK.
Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
Child Neurology and Development Center, Hillel-Yaffe Medical Center, Hadera, Israel.


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.


PTRH2 gene; peripheral neuropathy; sensorineural hearing loss

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