BACKGROUND Methylmalonic acidemia (MMA), which is an autosomal recessive metabolic disorder, is caused by mutations in methylmalonyl-CoA mutase (MUT) gene. As a result, the conversion of methylmalonyl-CoA to succinyl-CoA is impaired in this disorder, leading to a wide range of clinical manifestations varying from no signs or symptoms to severe lethargy and metabolic crisis in newborn infants. Since identification of novel mutations in MUT gene can help discover the exact pathogenesis of MMA and also use these disease-causing mutations in prenatal diagnosis, this study was conducted to uncover the possible mutations in an Iranian couple with a deceased offspring clinically diagnosed as having organic acidemia. Moreover, to prevent the occurrence of the mutation in the next pregnancy, we took the advantage of pre-implantation genetic diagnosis (PGD), which resulted in a successful pregnancy. CASE PRESENTATION The affected individual was a 15-month-old boy who passed away due to aspiration pneumonia. The child presented at the age of 3 months with lethargy, protracted vomiting, hypotonia, and decreased level of consciousness. To find the mutated gene, Next Generation Sequencing (NGS) was performed as carrier testing for the parents and the results revealed a novel (private) heterozygous missense mutation in MUT gene (c.1055A > G, p.Q352R). After performing PGD on three blastomeres, one was identified as being homozygous wild-type that was followed by successful pregnancy. CONCLUSIONS Our study identified a novel, deleterious, heterozygous missense mutation in MUT gene in a couple and helps to consider the genetic counselling and prenatal diagnosis more seriously for this family with clinical phenotypes of organic acidemia.

中文翻译：

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具有MUT基因新突变的伊朗家庭的植入前遗传学诊断。

背景技术甲基丙二酸血症（MMA）是一种常染色体隐性代谢障碍，是由甲基丙二酰-CoA突变酶（MUT）基因的突变引起的。结果，在这种疾病中，甲基丙二酰辅酶A向琥珀酰辅酶A的转化受到损害，导致了广泛的临床表现，从无体征或症状到严重的嗜睡和新生儿代谢危急。由于鉴定MUT基因中的新突变可以帮助发现MMA的确切发病机理，并且还可以在产前诊断中使用这些致病突变，因此进行了这项研究，以发现伊朗夫妇中已被诊断为患有器质性疾病的后代的可能突变。酸血症。此外，为了防止下次怀孕发生突变，我们利用了植入前基因诊断（PGD）的优势，导致成功怀孕。病例介绍受影响的个体是一个15个月大的男孩，他因吸入性肺炎而去世。该孩子在3个月大时表现出嗜睡，长期呕吐，肌张力低下和意识下降。为了找到突变的基因，对父母进行了下一代测序（NGS）作为载体测试，结果揭示了MUT基因中一个新的（私人）杂合错义突变（c.1055A> G，p.Q352R）。在对三个卵裂球进行PGD后，其中一个被鉴定为纯合野生型，随后成功怀孕。结论我们的研究确定了一种新颖的，有害的，