Luo Jianhua, Wang Qingming, Cheng Shuangxi, Chen Aixin, Yuan Haiming
Prenatal Diagnostic Center, Dongguan Maternal and Child Health Care Hospital, Dongguan, Guangdong 523120, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Sep 10;38(9):861-864. doi: 10.3760/cma.j.cn511374-20200929-00701.
To explore the genotype-phenotype correlation in a child with Kabuki syndrome type 1 (KS1) caused by a mosaic frameshift variant of KMT2D gene.
Trio-based whole exome sequencing (WES) was carried for the patient and her parents. Candidate variant was verified by Sanger sequencing.
The proband, a 3-year-and-2-month-old Chinese girl, presented with distinctive facial features, cognitive impairment, mild developmental delay, dermatoglyphic abnormalities, minor skeletal anomalies, ventricular septal defect, and autistic behavior. Trio-based WES revealed that the proband has carried a de novo mosaic frameshit variant of the KMT2D gene, namely NM_003482.3:c.13058delG (p.Pro4353Argfs*31) (GRCh37/hg19), for which the mosaicism rate was close to 21%. The variant was unreported previously and was confirmed by Sanger sequencing. Chromosomal microarray analysis (CMA) has revealed no pathogenic or likely pathogenic copy number variations. Compared with previously reported cases, our patient has presented obvious behavior anomalies including autism, anxiety and sleep problems, which were rarely reported.
This study has expanded the spectrum of KMT2D gene variants, enriched the clinical phenotypes of KS1, and facilitated genetic counseling for the family.
探讨由KMT2D基因的嵌合移码变异导致的1型歌舞伎综合征（KS1）患儿的基因型-表型相关性。
对该患者及其父母进行基于三联体的全外显子组测序（WES）。候选变异通过桑格测序进行验证。
先证者为一名3岁2个月大的中国女孩，具有独特的面部特征、认知障碍、轻度发育迟缓、皮纹异常、轻微骨骼异常、室间隔缺损和自闭症行为。基于三联体的WES显示，先证者携带KMT2D基因的一个新生嵌合移码变异，即NM_003482.3:c.13058delG（p.Pro4353Argfs*31）（GRCh37/hg19），其嵌合率接近21%。该变异此前未被报道，并通过桑格测序得到证实。染色体微阵列分析（CMA）未发现致病性或可能致病性的拷贝数变异。与先前报道的病例相比，我们的患者表现出明显的行为异常，包括自闭症、焦虑和睡眠问题，这些情况很少被报道。
本研究扩展了KMT2D基因变异谱，丰富了KS1的临床表型，并为该家庭提供了遗传咨询。
