Ataxia and cerebellar anomalies - narrow panel

Gene: PTRH2

Green List (high evidence)

Comment on list classification: There are at least five unrelated families with IMNEPD presented with ataxia 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: 24 Oct 2025, 5:11 p.m. | Last Modified: 24 Oct 2025, 5:11 p.m.

Panel Version: 8.30

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. Ataxia was present in the Tunisian patient and in three of four Saudi Arabian 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 of them had ataxia.

This gene has been associated with IMNEPD in OMIM (MIM #616263, OMIM accessed on 24 October 2025), which includes ataxia as one of the clinical manifestations present in most patients. This gene is also associated with a green rating on Ataxia - paediatric panel of PanelApp Australia (https://panelapp-aus.org/panels/271/gene/PTRH2/)

Created: 24 Oct 2025, 5:07 p.m. | Last Modified: 24 Oct 2025, 5:07 p.m.

Panel Version: 8.27

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

Green List (high evidence)

New gene suggested by Genomics England clinical team memeber- unable to do a full curational review (Green rating recommended) as we are waiting for new PanelApp features before this gene can be added to this GMS panel.

Created: 22 Jan 2020, 11:46 a.m. | Last Modified: 22 Jan 2020, 11:46 a.m.

Panel Version: 2.0

Green List (high evidence)

Currently on adult ataxia panel; more suitable for childhood onset panel
Sources: Other

Created: 12 Dec 2019, 10:02 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile-onset multisystem neurologic, endocrine, and pancreatic disease

Publications

• 25574476
• 28328138