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, с.471_473delCGA, c.161 T > C (p.Leu54Pro), c.531C > A (р.Phe177Leu), c.647C > T (p.Ser216Leu), c.705G > A (р.Gly235Asp), c.898 G > A (р.Gly300Ser), c.1205G > C (р.Arg402Pro), c.1178G > A (р.Gly393Glu). The most commonly detected missense variants were c.1204C > T (p.Arg402Trp) and с.1262C > T (р.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.

中文翻译：

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49 个俄罗斯家族中 1 型戊二酸尿症的分子和生化研究：GCDH 基因中的九个新突变。

1 型戊二酸尿症（GA1，戊二酰辅酶 A 脱氢酶缺乏症，1 型戊二酸血症）（ICD-10 代码：E72.3；MIM 231670）是一种常染色体隐性疾病，由编码戊二酰辅酶 A 脱氢酶 (GCDH) 的基因突变引起）。在此，我们介绍了来自俄罗斯 49 个无关家庭的 51 名诊断为 GA1 的患者的生化和分子遗传特征。我们共鉴定了 21 个变体，其中 9 个是新的：c.127 + 1G > T、с.471_473delCGA、c.161 T > C (p.Leu54Pro)、c.531C > A (р.Phe177Leu)、c .647C > T (p.Ser216Leu), c.705G > A (р.Gly235Asp), c.898 G > A (р.Gly300Ser), c.1205G > C (р.Arg402Pro), c.1178G > A ( р.Gly393Glu)。最常检测到的错义变体是 c.1204C > T (p.Arg402Trp) 和 с.1262C > T (р.Ala421Val)，它们的识别率分别为 56.38% 和 11。7% 的突变等位基因。在两名患者中检测到 19 号染色体短臂 (p) 位置 12,994,984-13,003,217 (8233 bp) 和位置 12,991,506-13,003,217 (11,711 bp) 的杂合微缺失。位于失衡区域的基因为 KLF1、DNASE2 和 GCDH。除了一名具有纯合突变 p.Val400Met 的患者外，患者在生物体液中表现出典型的 GA1 生化变化。在我们的患者队列中未发现 GCDH 基因型与戊二酸 (GA) 浓度之间存在相关性。除了一名具有纯合突变 p.Val400Met 的患者外，患者在生物体液中表现出典型的 GA1 生化变化。在我们的患者队列中未发现 GCDH 基因型与戊二酸 (GA) 浓度之间存在相关性。除了一名具有纯合突变 p.Val400Met 的患者外，患者在生物体液中表现出典型的 GA1 生化变化。在我们的患者队列中未发现 GCDH 基因型与戊二酸 (GA) 浓度之间存在相关性。