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BMC Med Genet. 2018 Sep 14;19(1):167. doi: 10.1186/s12881-018-0675-9.

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

Peng W1,2,3, Ma XW1,2,3, Yang X1,2,3, Zhang WQ1,2,3, Yan L1,2,3, Wang YX1,2,3, Liu X1,2,3, Wang Y4,5,6, Feng ZC7,8,9.

Author information

1
Baiyi Children's Hospital affiliated to PLA Army General Hospital, Beijing, 100700, People's Republic of China.
2
National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, 100700, People's Republic of China.
3
Beijing Key Laboratory of Pediatric Organ Failure, Beijing, 100700, People's Republic of China.
4
Baiyi Children's Hospital affiliated to PLA Army General Hospital, Beijing, 100700, People's Republic of China. 001wangyan@sina.com.
5
National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, 100700, People's Republic of China. 001wangyan@sina.com.
6
Beijing Key Laboratory of Pediatric Organ Failure, Beijing, 100700, People's Republic of China. 001wangyan@sina.com.
7
Baiyi Children's Hospital affiliated to PLA Army General Hospital, Beijing, 100700, People's Republic of China. zhichunfeng81@163.com.
8
National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, 100700, People's Republic of China. zhichunfeng81@163.com.
9
Beijing Key Laboratory of Pediatric Organ Failure, Beijing, 100700, People's Republic of China. zhichunfeng81@163.com.

Abstract

BACKGROUND:

L-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 PRESENTATION:

We 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.

CONCLUSION:

We 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.

KEYWORDS:

L-2-Hydroxyglutaric aciduria; L2HGDH; Mutation

PMID:
30217188
PMCID:
PMC6137868
DOI:
10.1186/s12881-018-0675-9
[Indexed for MEDLINE]
Free PMC Article

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