Monogenic hearing loss

Gene: PTRH2

Green List (high evidence)

Comment on list classification: There are at least eight unrelated families with IMNEPD presented with sensorineural hearing loss as part of the phenotype. Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 27 Oct 2025, 11:36 a.m. | Last Modified: 27 Oct 2025, 11:36 a.m.

Panel Version: 5.39

PMID:25574476 (2014) reported a consanguineous family of Yazidian-Turkish descent infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). The two affected children presented with intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. They were identified with a homozygous frameshift variant in PTRH2 gene.

PMID:25558065 (2015) reported a patient with global developmental delay, hearing loss, and ataxia and was identified with a homozygous missense variant PTRH2 gene.

PMID:27129381 (2016) reported the identification of a different homozygous missense variant in five further IMNEPD patients from two different families of Tunisian and Saudi Arabian descent. Sensorineural hearing impairment was present in all five reported patients.

PMID:31057140 (2019) reported three brothers of Syrian descent with a novel homozygous stop-gain variant in PTRH2 gene presenting with IMNEPD. All three had hearing loss.

This gene has been associated with IMNEPD in OMIM (MIM #616263, OMIM accessed on 24 October 2025), which includes sensorineural deafness as one of the clinical manifestations. This gene is also associated with relevant phenotypes on the DD panel of Gene2Phenotype with 'definitive' rating.
Sources: Literature

Created: 27 Oct 2025, 11:34 a.m. | Last Modified: 27 Oct 2025, 11:35 a.m.

Panel Version: 5.38

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, OMIM:616263; neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1, MONDO:8000012

Publications

• 25574476
• 25558065
• 27129381
• 31057140