Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria

Abstract

BackgroundL-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons.Case presentationWe presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic.ConclusionWe predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations.

A novel protein truncating mutation in L2HGDH causes L-2-hydroxyglutaric aciduria in a consanguineous Pakistani family

“…However, tonic-clonic seizure and macrocephaly was not present in the patients presented here. Further, Peng et al (2018) have reported a few missense and frameshift mutations in Chinese patients, who exhibited mild phenotypes comparable to the patients included in the current study (Peng et al…”

Spectrum of Organic Aciduria Diseases in Tunisia: A 35-year Retrospective Study

“…Furthermore, the disease does not present an acute deterioration course, which leads to a delayed clinical diagnosis in childhood, as most patients can live to adulthood. [ 43 ] The incidence also varies according to the detection capability of each center, which is influenced by the expertise of the medical team, technology, and methods available for the screening and confirmatory tests, accessibility of patients to testing, as well as financial resources of the center and the country. [ 44 ] In the current study, the screening was selective and was based on familial history or clinical presentation.…”

Structure and biochemical characterization of l-2-hydroxyglutarate dehydrogenase and its role in the pathogenesis of l-2-hydroxyglutaric aciduria

“…This article contains supporting information ( 37 , 53 , 55 , 58 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ).…”