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| Intellectual disability - microarray and sequencing v3.1100 | RPIA | Arina Puzriakova Phenotypes for gene: RPIA were changed from ?Ribose 5-phosphate isomerase deficiency, 608611; Ribose 5-phosphate isomerase deficiency, MIM 608611. to Ribose 5-phosphate isomerase deficiency, OMIM:608611 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.978 | RPIA |
Catherine Snow Source Expert Review Green was added to RPIA. Source Expert Review was added to RPIA. Added phenotypes ?Ribose 5-phosphate isomerase deficiency, 608611 for gene: RPIA Publications for gene RPIA were changed from 14988808; 20499043; 28801340; 30088433 to 20499043; 31056085; 14988808; 30088433; 28801340 Rating Changed from No List (delete) to Green List (high evidence) |
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| Intellectual disability - microarray and sequencing v2.579 | RPIA |
Konstantinos Varvagiannis gene: RPIA was added gene: RPIA was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: RPIA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RPIA were set to 14988808; 20499043; 28801340; 30088433 Phenotypes for gene: RPIA were set to Ribose 5-phosphate isomerase deficiency, MIM 608611. Penetrance for gene: RPIA were set to unknown Review for gene: RPIA was set to GREEN gene: RPIA was marked as current diagnostic Added comment: Biallelic pathogenic variants in RPIA cause Ribose 5-phosphate isomerase deficiency, MIM 608611. PMID: 14988808 is the first report on the disorder with molecular (incl. genetic) confirmation of the diagnosis. A patient initially investigated for early developmental delay, leukoencephalopathy, seizures with onset at 4 years, with subsequent neurologic regression and peripheral neuropathy at the age of 7, was suspected to have a disorder of the pentose phosphate pathway on the basis of highly elevated polyols on brain MRS and body fluid analysis. Reduced ribose 5-phosphate isomerase activity was shown in fibroblasts. Genetic testing demonstrated the presence of a missense (NM_144563.2:c.404C>T / NP_653164.2:p.Ala135Val - previously referred to as A61V) as well as a frameshift variant (NM_144563.2:c.762delG / NP_653164.2:p.Asn255Ilefs). Additional extensive supportive functional studies were published a few years later (PMID: 20499043). [This patient was initially described in PMID: 10589548]. PMID: 28801340 is a report on a second patient. This individual presented with delayed early development (independent walking and speech achieved at 2 and 5 years respectively), seizures and regression at the age of 7 with MRI white matter abnormalities. Review of magnetic resonance spectroscopy (MRS) was suggestive of elevated polyols (arabitol and ribitol). In line with this, genetic testing revealed a homozygous missense variant in RPIA (NM_144563.2:c.592T>C or p.Phe198Leu). Urine analysis confirmed elevated excretion of polyols, thus confirming the diagnosis. PMID: 30088433 reports on a boy with neonatal onset leukoencephalopathy and developmental delay having undergone early metabolic testing and aCGH (the latter at the age of 16 months). Persistance of his delay motivated exome sequencing at the age of approx. 4.5 years which demonstrated 2 RPIA variants (NM_144563.2:c.253G>A or p.Ala85Thr and NM_144563.2:c.347-1G>A). Measurement of ribitol and arabitol in urine demonstrated significant elevations (>20x) consistent with this diagnosis. RPIA is included in gene panels for intellectual disability offered by various diagnostic laboratories. As a result this gene can be considered for inclusion in this panel as green (or amber). Sources: Literature |
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