Cui Yan, Zhang Yingxian, Fu Dongxia, Liu Xiaojing, Wei Haiyan
Department of Pediatric Endocrinology and Genetic Metabolism, the Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou Key Laboratory of Pediatric Endocrine, Genetic and Metabolism Diseases, Zhengzhou, Henan 450000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 May 10;38(5):481-484. doi: 10.3760/cma.j.cn511374-20200414-00267.
To explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature.
Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software.
The child was found to carry compound heterozygous missense variants of the ALPL gene, including c.1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c.1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+PM5+PP3+PP4).
The compound heterozygous variants of c.1130C>T (p.Ala377Val) and c.1300G>A (p.Val434Met) of the ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of ALPL gene variants.
探究一名患有骨与牙齿矿化障碍、乳牙早萌、佝偻病及身材矮小的女童的遗传基础。
提取基因组DNA并进行高通量全外显子组测序。通过桑格测序法确认可疑变异。使用生物信息学软件分析潜在变异的影响。
发现该患儿携带ALPL基因的复合杂合错义变异，包括c.1130C>T（p.A377V），这是一个从其父亲遗传而来的已知致病突变，以及c.1300G>A（p.V434M），此变异从其母亲遗传而来，此前未被报道，根据美国医学遗传学与基因组学学会的标准和指南（PM2+PM5+PP3+PP4）预测可能致病。
ALPL基因的c.1130C>T（p.Ala377Val）和c.1300G>A（p.Val434Met）复合杂合变异可能是该患儿疾病的病因。上述发现丰富了ALPL基因变异谱。
