Molecular and biochemical study of glutaric aciduria type 1 in 49 Russian families: nine novel mutations in the GCDH gene.
Metab Brain Dis
; 35(6): 1009-1016, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32240488
ABSTRACT
Glutaric aciduria type 1 (GA1, deficiency of glutaryl CoA dehydrogenase, glutaric acidemia type 1) (ICD-10 code E72.3; MIM 231670) is an autosomal recessive disease caused by mutations in the gene encoding the enzyme glutaryl CoA dehydrogenase (GCDH). Herein, we present the biochemical and molecular genetic characteristics of 51 patients diagnosed with GA1 from 49 unrelated families in Russia. We identified a total of 21 variants, 9 of which were novel c.127 + 1G > T, Ñ.471_473delCGA, c.161 T > C (p.Leu54Pro), c.531C > A (Ñ.Phe177Leu), c.647C > T (p.Ser216Leu), c.705G > A (Ñ.Gly235Asp), c.898 G > A (Ñ.Gly300Ser), c.1205G > C (Ñ.Arg402Pro), c.1178G > A (Ñ.Gly393Glu). The most commonly detected missense variants were c.1204C > T (p.Arg402Trp) and Ñ.1262C > T (Ñ.Ala421Val), which were identified in 56.38% and 11.7% of mutated alleles. A heterozygous microdeletion of the short arm (p) of chromosome 19 from position 12,994,984-13,003,217 (8233 b.p.) and from position 12,991,506-13,003,217 (11,711 b.p.) were detected in two patients. Genes located in the area of imbalance were KLF1, DNASE2, and GCDH. Patients presented typical GA1 biochemical changes in the biological fluids, except one patient with the homozygous mutation p.Val400Met. No correlation was found between the GCDH genotype and glutaric acid (GA) concentration in the cohort of our patients.
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Base de dados:
MEDLINE
Assunto principal:
Encefalopatias Metabólicas
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Mutação de Sentido Incorreto
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Glutaril-CoA Desidrogenase
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Erros Inatos do Metabolismo dos Aminoácidos
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Child, preschool
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Female
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Humans
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Infant
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Male
País como assunto:
Asia
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Europa
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article