Li Xiaoli, Jia Tianming, Zhang Xiaoli, Gan Ling, Guo Qiliang, Li Xiao
Department of Pediatric Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Feb 10;38(2):108-111. doi: 10.3760/cma.j.cn511374-20200216-00083.
To explore the genetic basis for three children with Menkes disease.
The patients were subjected to next-generation sequencing (NGS) to detect potential variants of the ATP7A gene. Suspected variants were verified by Sanger sequencing of their family members and 200 healthy individuals. Multiplex ligation-dependent probe amplification (MLPA) was also carried out to detect potential deletions in their family members and 20 healthy individuals.
Variants of the ATP7A gene were detected in all of the three families, including a novel c.1465A>T nonsense variant in family 1, a novel c.3039_3043del frame-shifting variant in family 2, and deletion of exons 3 to 23 in family 3, which was reported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.1465A>T and c.3039_3043del variants of ATP7A gene were predicted to be likely pathogenic (PVS1+PM2).
Variants of the ATP7A gene may underlay the Menkes disease in the three children. Above findings have facilitated clinical diagnosis and enriched the spectrum of genetic variants of Menkes disease.
探究3例门克斯病患儿的遗传基础。
对患者进行二代测序（NGS）以检测ATP7A基因的潜在变异。通过对其家庭成员和200名健康个体进行桑格测序来验证可疑变异。还进行了多重连接依赖探针扩增（MLPA）以检测其家庭成员和20名健康个体中的潜在缺失。
在所有3个家庭中均检测到ATP7A基因变异，包括家系1中一个新的c.1465A>T无义变异，家系2中一个新的c.3039_3043del移码变异，以及家系3中外显子3至23的缺失，后者曾有报道。根据美国医学遗传学与基因组学学会的标准和指南，ATP7A基因的c.1465A>T和c.3039_3043del变异被预测可能致病（PVS1+PM2）。
ATP7A基因变异可能是这3例患儿患门克斯病的病因。上述发现有助于临床诊断并丰富了门克斯病的遗传变异谱。
