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The relationship between beta-ureidopropionase deficiency due to UPB1 variants and human phenotypes is uncertain.
- Source :
-
Molecular Genetics & Metabolism . Sep2022, Vol. 137 Issue 1/2, p62-67. 6p. - Publication Year :
- 2022
-
Abstract
- Beta-ureidopropionase deficiency, caused by variants in UPB1 , has been reported in association with various neurodevelopmental phenotypes including intellectual disability, seizures and autism. We aimed to reassess the relationship between variants in UPB1 and a clinical phenotype. Literature review, calculation of carrier frequencies from population databases, long-term follow-up of a previously published case and reporting of additional cases. Fifty-three published cases were identified, and two additional cases are reported here. Of these, 14 were asymptomatic and four had transient neurological features; clinical features in the remainder were variable and included non-neurological presentations. Several of the variants previously reported as pathogenic are present in population databases at frequencies higher than expected for a rare condition. In particular, the variant most frequently reported as pathogenic, p.Arg326Gln, is very common among East Asians, with a carrier frequency of 1 in 19 and 1 in 907 being homozygous for the variant in gnomAD v2.1.1. Pending the availability of further evidence, UPB1 should be considered a 'gene of uncertain clinical significance'. Caution should be used in ascribing clinical significance to biochemical features of beta-ureidopropionase deficiency and/or UPB1 variants in patients with neurodevelopmental phenotypes. UPB1 is not currently suitable for inclusion in gene panels for reproductive genetic carrier screening. The relationship between beta-ureidopropionase deficiency due to UPB1 variants and clinical phenotypes is uncertain. • The relationship between damaging UPB1 variants and human phenotypes is uncertain. • Described beta-ureidopropionase deficiency cases do not have a consistent phenotype. • Loss of function UPB1 variants are common in the general population. • Care must be used in ascribing diagnostic value to variants in UPB1. • UPB1 should not be included on carrier screening panels. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10967192
- Volume :
- 137
- Issue :
- 1/2
- Database :
- Academic Search Index
- Journal :
- Molecular Genetics & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 159821837
- Full Text :
- https://doi.org/10.1016/j.ymgme.2022.07.011