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Intellectual disability

Gene: PTRHD1

Amber List (moderate evidence)

PTRHD1 (peptidyl-tRNA hydrolase domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000184924
EnsemblGeneIds (GRCh37): ENSG00000184924
OMIM: 617342, Gene2Phenotype
PTRHD1 is in 1 panel

2 reviews

Catherine Snow (Genomics England)

Comment on list classification: Konstantinos Varvagiannis submitted an Amber review for PTRHD1. OMIM has rated this as VUS (last update : 02/23/2017) based on papers (PMID: 27134041, 27753167) involving two separate variants from two Iranian families. Kuipers et al. (PMID: 30398675) report on 3 individuals of African origin with identical phenotype with a homozygous for a frameshift PTRHD1 deletion. Limited information provided on ID therefore adding to watchlist and rating as Amber
Created: 30 May 2019, 9:15 a.m.

Konstantinos Varvagiannis (Other)

I don't know

7 individuals with biallelic PTRHD1 mutations from 3 pedigrees have been reported. The phenotype in all consisted of early-onset Parkinsonism with intellectual disability (overview in Table 1 - PMID: 30398675).

Jaberi et al. (PMID: 27134041) first reported on 2 sibs born to consanguineous Iranian parents. Both presented with parkinsonism with ID. After homozygosity mapping and exome sequencing, one variant in PTRHD1 (NM_001013663.1:c.155G>A or p.Cys52Tyr) as well as another variant in ADORA1 were the only candidates for the patients phenotype. At the time, the authors favored ADORA1 as the causative gene for their patients' phenotype but could not exclude pathogenicity of PTRHD1.

Khodadadi et al. (PMID: 27753167) published on 2 additional sibs from Iran with a similar phenotype. These individuals - born to consanguineous parents - were homozygous for a further PTRHD1 missense variant (p.His53Tyr) which is proximal to the variant reported by Jaberi et al.

This led the authors of the first publication to acknowledge that PTRHD1 was probably responsible for their patients' phenotype (PMID: 29143421). [A recent study of exome sequencing data of a Parkinson disease 1214-patient cohort failed to find any case explained by biallelic ADORA1 mutations - PMID: 27987235].

The variants reported in these 2 publications are classified as VUS in OMIM (last update : 02/23/2017).

Kuipers et al. (PMID: 30398675) report on 3 additional individuals of African origin with identical phenotype. These individuals, whose parents originated from an isolated african community, were homozygous for a frameshift PTRHD1 deletion (c.169_196del or p.Ala57Argfs*26). This variant is rare in gnomAD (MAF of 0.018% overall or 0.15% in the African subpopulation). Alternative causes of PD / parkinsonism were previously excluded.

The phenotype of all reported individuals is summarized in Table 1 of this article.

PTRHD1 is not assocated with any phenotype in OMIM nor in G2P.

This gene is included in the gene panel for ID, offered by Radboudumc.

Therefore, this gene can be considered for inclusion in this panel as amber or green.

[Please consider inclusion of this gene in the Parkinson Disease and Complex Parkinsonism gene panel].
Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 12 Dec 2018, 2:24 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Parkinsonism; Intellectual disability


Variants in this GENE are reported as part of current diagnostic practice


Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Amber
  • Expert Review
  • Expert Review Amber
  • Expert Review
  • Intellectual disability
  • Parkinsonism, Intellectual disability
  • Parkinsonism
Clinvar variants
Variants in PTRHD1
Panels with this gene

History Filter Activity

25 Jul 2019, Gel status: 2

Added Tag

Catherine Snow (Genomics England)

Tag watchlist tag was added to gene: PTRHD1.

25 Jul 2019, Gel status: 2

Added New Source, Added New Source, Set Phenotypes, Set publications, Status Update

Catherine Snow (Genomics England)

Source Expert Review was added to PTRHD1. Source Expert Review Amber was added to PTRHD1. Added phenotypes Parkinsonism, Intellectual disability for gene: PTRHD1 Publications for gene PTRHD1 were changed from 30398675; 27134041; 29143421; 27753167 to 30398675; 27134041; 27753167; 29143421 Rating Changed from No List (delete) to Amber List (moderate evidence)

12 Dec 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: PTRHD1 was added gene: PTRHD1 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: PTRHD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTRHD1 were set to 30398675; 27134041; 29143421; 27753167 Phenotypes for gene: PTRHD1 were set to Parkinsonism; Intellectual disability Penetrance for gene: PTRHD1 were set to Complete Review for gene: PTRHD1 was set to AMBER gene: PTRHD1 was marked as current diagnostic