Entire FGF12 duplication by complex chromosomal rearrangements associated with West syndrome
Entire FGF12 duplication by complex chromosomal rearrangements associated with West syndrome
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DOI：
10.1038/s10038-019-0641-1
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发表时间：
2019-10-01
影响因子：
3.5
通讯作者：
Matsumoto, Naomichi
中科院分区：
文献类型：
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作者：
Oda, Yoichiro;Uchiyama, Yuri;Matsumoto, Naomichi
在1例严重癫痫、发育迟缓、面部畸形和骨骼异常的患者中发现3号和9号染色体的复杂重排。分子细胞遗传学分析显示46，XX。Ish der(9)(3qter->；3q28：：9p21.1->；9p22.3：：9p22.3->；9qter)(RP11-368G14+，RP11-299O8-，RP11-905L2++，RP11-775E6++)。她的畸形特征与3q29微重复综合征和inv dup del(9p)相一致。基于Trio的WES没有发现致病的单核苷酸变异导致癫痫，但证实了涉及FGF12的3q28q29重复，FGF12编码成纤维细胞生长因子12。FGF12正向调节电压门控钠通道的活性。最近，在10例严重早发性癫痫患者中，仅发现一例复发的FGF12基因[NM_021032.4：c.341G>；A：p.(Arg114His)]。我们认为，患者的FGF12的完整复制可能类似于该患者癫痫表型中的FGF12的功能获得变异。
Complex rearrangements of chromosomes 3 and 9 were found in a patient presenting with severe epilepsy, developmental delay, dysmorphic facial features, and skeletal abnormalities. Molecular cytogenetic analysis revealed 46, XX. ish der(9) (3qter -> 3q28::9p21.1 -> 9p22.3::9p22.3 -> 9qter)(RP11-368G14+, RP11-299O8-, RP11-905L2++, RP11-775E6++). Her dysmorphic features are consistent with 3q29 microduplication syndrome and inv dup del(9p). Trio-based WES of the patient revealed no pathogenic single nucleotide variants causing epilepsy, but confirmed a 3q28q29 duplication involving FGF12, which encodes fibroblast growth factor 12. FGF12 positively regulates the activity of voltage-gated sodium channels. Recently, only one recurrent gain-of-function variant [NM_021032.4:c.341G>A:p.(Arg114His)] in FGF12 was found in a total of 10 patients with severe early-onset epilepsy. We propose that the patient's entire FGF12 duplication may be analogous to the gain-of-function variant in FGF12 in the epileptic phenotype of this patient.