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| Intellectual disability - microarray and sequencing v5.514 | PTRHD1 | Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v5.514 | PTRHD1 | Arina Puzriakova Phenotypes for gene: PTRHD1 were changed from Intellectual disability; Parkinsonism to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v5.513 | PTRHD1 | Arina Puzriakova Tag gene-checked was removed from gene: PTRHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1564 | PTRHD1 | Arina Puzriakova Tag gene-checked tag was added to gene: PTRHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1510 | PTRHD1 | Arina Puzriakova Tag for-review was removed from gene: PTRHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1510 | PTRHD1 | Sarah Leigh commented on gene: PTRHD1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1509 | PTRHD1 |
Arina Puzriakova Source Expert Review Green was added to PTRHD1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Intellectual disability - microarray and sequencing v3.472 | PTRHD1 | Arina Puzriakova Classified gene: PTRHD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.472 | PTRHD1 | Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.472 | PTRHD1 | Arina Puzriakova Gene: ptrhd1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.471 | PTRHD1 | Arina Puzriakova Tag for-review tag was added to gene: PTRHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.65 | PTRHD1 | Helen Brittain Marked gene: PTRHD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.65 | PTRHD1 | Helen Brittain Added comment: Comment when marking as ready: Further case from personal correspondence. Considered sufficient for a green rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.65 | PTRHD1 | Helen Brittain Gene: ptrhd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.65 | PTRHD1 | Helen Brittain Phenotypes for gene: PTRHD1 were changed from Intellectual disability; Parkinsonism, Intellectual disability; Parkinsonism to Intellectual disability; Parkinsonism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.64 | PTRHD1 | Helen Brittain Classified gene: PTRHD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.64 | PTRHD1 | Helen Brittain Gene: ptrhd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.63 | PTRHD1 | Helen Brittain Tag watchlist was removed from gene: PTRHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.63 | PTRHD1 | Helen Brittain Classified gene: PTRHD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.63 | PTRHD1 | Helen Brittain Gene: ptrhd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.63 | PTRHD1 | Helen Brittain Classified gene: PTRHD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.63 | PTRHD1 | Helen Brittain Gene: ptrhd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.62 | PTRHD1 | Helen Brittain reviewed gene: PTRHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.981 | PTRHD1 | Catherine Snow Tag watchlist tag was added to gene: PTRHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.978 | PTRHD1 |
Catherine Snow 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) |
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| Intellectual disability - microarray and sequencing v2.584 | PTRHD1 |
Konstantinos Varvagiannis 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 Added comment: 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 |
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