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| Undiagnosed metabolic disorders v1.495 | CLPB | Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.369 | STS | Catherine Snow Added comment: Comment on publications: There are >3 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.369 | STS | Catherine Snow Publications for gene: STS were set to 27604308; 1539590; 29672931 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.368 | STS |
Catherine Snow changed review comment from: Comment on list classification: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.; to: Comment on list classification: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. |
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| Undiagnosed metabolic disorders v1.368 | STS | Catherine Snow Publications for gene: STS were set to 27604308 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.367 | STS | Catherine Snow Classified gene: STS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.367 | STS | Catherine Snow Gene: sts has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.366 | STS | Catherine Snow reviewed gene: STS: Rating: GREEN; Mode of pathogenicity: None; Publications: 1539590, 29672931; Phenotypes: Ichthyosis, X-linked, 308100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.209 | NDUFB9 | Sarah Leigh Added comment: Comment on publications: PMID: 22200994 Reports one probound heterozygous for a variant (c.140G>T, p.Arg47Leu) within NDUFB9 with parents not available for genetic testing, and in vitro complement studies in patient fibroblasts showed wildtype NDUFB9 did not rescue complex I activity, therefore was deemed not pathogenic. Reports two brothers homozygous for a variant in the gene, with parents who are heterozygous carriers (c.191T>C, p.Leu64Pro). In vitro, fibroblasts from the proband showed low complex I activity, and wildtype NDUFB9 rescued complex I activity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.82 | RPIA |
Sarah Leigh commented on gene: RPIA: Review by Konstantinos Varvagiannis for the Genetic Epilepsy syndromes panel. 9 Dec 2018, 1:44 a.m. Panel version: 0.1488 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 or p.Ala135Val - previously referred to as A61V) as well as a frameshift variant (NM_144563.2:c.762delG or 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. 2 of the 3 patients described in the literature presented seizures. As a result this gene can be considered for inclusion in this panel as amber. [This gene is also present in the Undiagnosed metabolic disorders gene panel as red. Please consider upgrade based on these further publications.]. Sources: Literature |
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| Undiagnosed metabolic disorders | STS | Sarah Leigh commented on STS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders | STS | Sarah Leigh reviewed STS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||