KMT2D基因变异所致歌舞伎综合征1例

doi:10.6040/j.issn.1671-7554.0.2023.1041

摘要/Abstract

摘要： 目的探讨歌舞伎综合征(Kabuki syndrome, KS)临床表型及基因变异类型和基因检测诊断。方法对患儿进行外周血家系全外显子测序,并通过Sanger DNA测序验证。结果先证者为6岁5个月的女性患儿,表现为特殊面容、发育迟缓、惊厥发作、脑电图异常、反复中耳炎病史等。患儿外周血家系全外显子测序显示,KMT2D基因(NM003482)c.3094del(p.Leu1032TrpfsTer24)存在变异。该变异为移码变异。Sanger DNA测序结果显示患儿父亲、母亲均未携带该变异,表明该变异为新发变异。根据美国医学遗传学与基因组学学会变异解读标准,该基因变异分类为 PVS1+PS2+PM2,属于致病性变异。结论患儿确诊为由KMT2D基因变异导致 KS1型,为常染色体显性遗传。本研究结果表明,对于疑似KS者应做到早诊断、早干预;对于已知基因无变异的患者,应根据国际共识标准进行临床诊断,并进行随访和遗传咨询。本研究进一步丰富了KS基因变异谱,为该病的诊断和遗传咨询提供依据。

关键词: 歌舞伎综合征, KMT2D基因, 特殊面容, 家系基因检测

Abstract: Objective To explore the clinical phenotype, gene variant types and diagnosis of genetic testing of Kabuki syndrome(KS). Methods The whole exon sequencing(WES)of peripheral blood of a child was performed and verified with Sanger DNA sequencing. Results The proband was a girl aged 6 years and 5 months, who showed special facial features, developmental delay, convulsive seizures, abnormal electroencephalogram, and recurrent otitis media. WES showed KMT2D gene(NM003482)c.3094del,(p.Leu1032TrpfsTer24)mutation, which was a frameshift mutation. Sanger DNA sequencing results showed that the father and mother of the proband did not carry the KMT2D mutation, indicating that this mutation was a de novo one. According to the(American College of Medical Genetics and Genomics, ACMG)mutation interpretation standard, the mutation was classified as PVS1+PS2+PM2, which was a pathogenic mutation of KS. Conclusion The child was diagnosed with KS type 1 caused by KMT2D gene mutation, which was autosomal dominant. Our study revealed that early diagnosis and intervention should be performed for suspected KS; for patients with no known genetic variation, clinical diagnosis should be confirmed according to international consensus criteria, follow-up and genetic counseling. This study enriched the genetic mutation spectrum of KS and provided a basis for the diagnosis and genetic counseling of this disease.

Key words: Kabuki syndrome, KMT2D gene, Special facial features, Trio-whole genome testing

中图分类号:

R725

董佳宁,张飘飘,徐芬芬,赵红洋. KMT2D基因变异所致歌舞伎综合征1例[J]. 山东大学学报 (医学版), 2024, 62(2): 90-95.

DONG Jianing, ZHANG Piaopiao, XU Fenfen, ZHAO Hongyang. A case of Kabuki syndrome caused by KMT2D gene mutation[J]. Journal of Shandong University (Health Sciences), 2024, 62(2): 90-95.

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