Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
RILD Wellcome Wolfson Centre - Level 4, Royal Devon and Exeter NHS Foundation Trust, University of Exeter Medical School, Barrack Road, Exeter, EX2 5DW, UK.
BMC Med Genet. 2018 Feb 20;19(1):25. doi: 10.1186/s12881-018-0532-x.
L-2-hydroxyglutaric aciduria (L2HGA) is a progressive neurometabolic disease of brain caused by mutations of in L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene. Cardinal clinical features include cerebellar ataxia, epilepsy, neurodevelopmental delay, intellectual disability, and other clinical neurological deficits.
We describe an index case of the family presented with generalised tonic-clonic seizure, developmental delay, intellectual disability, and ataxia. Initially, the differential diagnosis was difficult to be established and a SNP genome wide scan identified the candidate region on chromosome 14q22.1. DNA sequencing showed a novel homozygous mutation in the candidate gene L2HGDH (NM_024884.2: c.178G > A; p.Gly60Arg). The mutation p.Gly60Arg lies in the highly conserved FAD/NAD(P)-binding domain of this mitochondrial enzyme, predicted to disturb enzymatic function.
The combination of homozygosity mapping and DNA sequencing identified a novel mutation in Pakistani family with variable clinical features. This is second report of a mutation in L2HGDH gene from Pakistan and the largest family with L2HGA reported to date.
L-2-羟戊二酸尿症（L2HGA）是一种由 L-2-羟戊二酸脱氢酶（L2HGDH）基因突变引起的进行性脑神经代谢疾病。主要临床特征包括小脑共济失调、癫痫、神经发育迟缓、智力障碍和其他临床神经功能缺陷。
我们描述了一个家系的首发病例，表现为全面强直阵挛发作、发育迟缓、智力障碍和共济失调。最初，鉴别诊断较为困难，SNP 全基因组扫描确定了 14q22.1 染色体上的候选区域。DNA 测序显示候选基因 L2HGDH（NM_024884.2：c.178G>A；p.Gly60Arg）中存在一个新的纯合突变。突变 p.Gly60Arg 位于该线粒体酶的高度保守的 FAD/NAD(P)-结合结构域，预计会干扰酶的功能。
纯合性作图和 DNA 测序相结合，在一个具有不同临床特征的巴基斯坦家系中鉴定出一个新的突变。这是巴基斯坦 L2HGDH 基因突变的第二份报告，也是迄今为止报道的最大的 L2HGA 家系。
