首页|MORC2基因新发变异导致DIGFAN综合征1例的遗传学分析

MORC2基因新发变异导致DIGFAN综合征1例的遗传学分析

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目的 探讨1例发育迟缓、生长落后、面部畸形和轴突神经病变(DIGFAN)患儿的临床表现和遗传学病因。 方法 选取2021年3月22日因"身材矮小、智力发育落后"就诊于广西医科大学第二附属医院儿童内分泌遗传代谢门诊的1例患儿作为研究对象，收集其临床资料。采集患儿及其父母的外周血样，进行全外显子组测序，确定候选变异，并对其家系进行Sanger测序验证。利用生物信息软件对变异位点进行致病性评估及蛋白模拟分析。 结果 患儿为10岁9月龄男性，存在身材矮小、智力发育落后、语言和运动发育迟缓、面部畸形等临床特征。基因测序提示患儿MORC2基因存在c.800T>C(p.Leu267Pro)杂合变异，Sanger测序验证为新发变异。该变异所在的氨基酸Leu267在不同物种间高度保守。Leu267位于MORC2蛋白的ATP酶结合区的核糖体蛋白S5结构域，Leu267Pro可能通过影响ATP酶的空间构象和活性，从而影响MORC2蛋白的功能。根据美国医学遗传学与基因组学学会基因变异评级相关指南，c.800T>C评级为可能致病性变异(PS2＋PM2_Supporting＋PP2＋PP3)。 结论 MORC2基因c.800T>C(p.Leu267Pro)变异考虑为该DIGFAN患儿的遗传学病因。 Objective To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN). Methods A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of theMORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.
Genetic analysis of a child with DIGFAN syndrome due to variant ofMORC2 gene
Objective To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN). Methods A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of theMORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.

Narvous system diseasesDevelopmental delayImpaired growthDysmorphic faciesAxonal neuropathyMORC2 geneDe novo variantChild

谢波波、范歆、魏贤达、桂宝恒、韦小娇、马云婷、俸诗瀚、陈玉君、许芯

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广西医科大学第二附属医院遗传与基因组医学中心，南宁　530007

2广西医科大学第二附属医院广西卫健委医学遗传与基因组学研究重点实验室，南宁　530007

广西医科大学第二附属医院广西卫健委医学遗传与基因组学研究重点实验室，南宁　530007

3广西医科大学第二附属医院儿科，南宁　530007

广西医科大学第二附属医院儿科，南宁　530007

4广西医科大学第二临床医学院，南宁　530007

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神经系统疾病 发育迟缓 生长落后 面部畸形 轴突神经病变 MORC2基因 新发变异 儿童

广西自然科学基金广西壮族自治区医疗卫生自筹课题广西壮族自治区医疗卫生自筹课题

2021GXNSFAA196047Z20210483Z20200669

2024

10.3760/cma.j.cn511374-20221205-00841

中华医学遗传学杂志
中华医学会

中华医学遗传学杂志

CSTPCD
影响因子：0.562
ISSN：1003-9406
年,卷(期)：2024.41(2)
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