Molecular genetics and metabolism · 2022
The relationship between beta-ureidopropionase deficiency due to UPB1 variants and human phenotypes is uncertain.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Righetti Sarah, Allcock Richard J N, Yaplito-Lee Joy, Adams Louisa, Ellaway Carolyn, Jones Kristi J, Selvanathan Arthavan, Fletcher Janice, Pitt James, van Kuilenburg André B P, Delatycki Martin B, Laing Nigel G, Kirk Edwin P
Аннотация
BACKGROUND: Beta-ureidopropionase deficiency, caused by variants in UPB1, has been reported in association with various neurodevelopmental phenotypes including intellectual disability, seizures and autism.
AIM: We aimed to reassess the relationship between variants in UPB1 and a clinical phenotype.
METHODS: Literature review, calculation of carrier frequencies from population databases, long-term follow-up of a previously published case and reporting of additional cases.
RESULTS: 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.
CONCLUSION: 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.
SYNOPSIS: The relationship between beta-ureidopropionase deficiency due to UPB1 variants and clinical phenotypes is uncertain.
AIM: We aimed to reassess the relationship between variants in UPB1 and a clinical phenotype.
METHODS: Literature review, calculation of carrier frequencies from population databases, long-term follow-up of a previously published case and reporting of additional cases.
RESULTS: 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.
CONCLUSION: 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.
SYNOPSIS: The relationship between beta-ureidopropionase deficiency due to UPB1 variants and clinical phenotypes is uncertain.