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| Intellectual disability - microarray and sequencing v2.981 | PTRH2 | Catherine Snow Tag watchlist tag was added to gene: PTRH2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.978 | PTRH2 |
Catherine Snow Source Expert Review was added to PTRH2. Source Expert Review Amber was added to PTRH2. Added phenotypes Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, 616263 for gene: PTRH2 Publications for gene PTRH2 were changed from 25574476; 27129381; 25558065; 28328138; 28175314 to 25574476; 28175314; 28328138; 25558065; 27129381 Rating Changed from No List (delete) to Amber List (moderate evidence) |
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| Intellectual disability - microarray and sequencing v2.588 | PTRH2 |
Konstantinos Varvagiannis gene: PTRH2 was added gene: PTRH2 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: PTRH2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTRH2 were set to 25574476; 27129381; 25558065; 28328138; 28175314 Phenotypes for gene: PTRH2 were set to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (MIM 616263) Penetrance for gene: PTRH2 were set to Complete Review for gene: PTRH2 was set to GREEN gene: PTRH2 was marked as current diagnostic Added comment: Biallelic pathogenic variants in PTRH2 cause Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (MIM 616263). Several affected individuals have been reported to date. ID was a feature in the majority. Hu et al. (2014 - PMID:25574476) reported on 2 sibs born to consanguineous Yazidian-Turkish family, homozygous for a frameshift variant [NM_016077.4(PTRH2):c.269_270delCT (p.Ala90Glyfs)]. In PMID: 27129381 (2016) the same group reported on 5 additional individuals, from 2 unrelated consanguineous (Tunesian / Saudi-Arabian) pedigrees. These subjects were homozygous for a missense variant [NM_016077.4(PTRH2):c.254A>C (p.Gln85Pro)]. A summary of the features observed in all 7 cases is provided in table 1 of the latter article. ID was a feature in all 6 individuals for whom this information was available (6/7). Phenotypic variability even among individuals with the same variant is underscored. mRNA studies for both variants have shown similar levels compared to controls, with reduced protein upon Western blot (for both). In Ptrh2-null mouse model a similar to the human phenotype is observed (muscle weakness and wasting, ataxia, cerebelar atrophy, etc.) (PMIDs:25574476 and 28175314). Alazami et al. (PMID: 25558065 - 2015) report on an additional individual homozygous for the p.Gln85Pro variant. This boy presented with intellectual disability (clinical details provided in the supplement). Sharkia et al. (PMID: 28328138) describe 3 sibs homozygous for the p.Gln85Pro variant. The index patient was reported to have normal intelligence upon formal testing which also appeared to be the case for her 2 sisters. Apart from the 2 variants observed in the published patients, 2 further variants have been submitted in ClinVar as likely pathogenic, namely : NM_016077.4(PTRH2):c.253C>T (p.Gln85Ter) and NM_001015509.2(PTRH2):c.114dup (p.Gly39Trpfs). PTRH2 is not associated with any phenotype in G2P. This gene is included in gene panels for intellectual disability offered by diagnostic laboratories (incl. Radboudumc). As a result it can be considered for inclusion in the ID panel as green (or amber). [As several individuals presented with ataxia, demyelinating sensorimotor neuropathy, sensorineural hearing loss and other possibly relevant phenotypes, consider inclusion in the respective gene panels]. Sources: Literature, Radboud University Medical Center, Nijmegen |
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