在一个罕见的中国人L-2-羟基戊二酸尿症家系中发现两个新的L2HGDH突变。

PubMed ID
发表日期 2018年09月

原始出处 医学遗传学
BMC medical genetics
作者 Peng  Wei  Ma  Xiu-Wei  Yang  Xiao  Zhang  Wan-Qiao  Yan  Lei  Wang  Yong-Xia  Liu  Xin  Wang  Yan  Feng  Zhi-Chun 

文献标题 在一个罕见的中国人L-2-羟基戊二酸尿症家系中发现两个新的L2HGDH突变。
Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria.

文献摘要 BACKGROUND

L-2-羟基戊二酸尿症(L-2-HGA)是一种罕见的器质性酸尿性神经代谢疾病,以常染色体隐性遗传方式遗传,有多种症状,如精神运动发育迟缓、癫痫、脑症状以及血浆中2-羟基戊二酸(2-HG)浓度升高,尿液和脑脊液。L-2-HGA的致病基因是L-2-羟基戊二酸脱氢酶基因(L2HGDH),由10个外显子组成。

CASE PRESENTATION

根据临床症状、磁共振成像(MRI)和气相色谱-质谱(GC-MS)结果,我们提出了一例罕见的L-2-HGA患者的初步诊断。对L-2-HGA患者及其父母进行了L2HGDH基因突变分析,发现外显子3有两个新的突变:纯合错义突变(c.407a) > G、 p.K136R),以及一个杂合移码突变[c.407a] > G、 c.408 del G],(p.K136SfsX3)在父系等位基因中。该蛋白的突变位点p.K136R位于FAD/NAD(p)结合域的口袋中,并被认为是致病的。

CONCLUSION

我们预测了纯合错义突变(c.407a) > G、 p.K136R)被认为是患者的致病突变。这项研究强调了系谱分析在解释新突变方面的作用。


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.


获取全文 10.1186/s12881-018-0675-9