首页|HECW2基因变异致神经发育迟滞1例的遗传学分析

HECW2基因变异致神经发育迟滞1例的遗传学分析

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目的 探讨1例神经发育迟滞患儿的分子遗传学病因。 方法 选取2022年5月9日因"发育迟滞、营养不良"就诊于甘肃省妇幼保健院的1例年龄为8月的女性患儿作为研究对象。收集患儿的临床资料,提取患儿及其父母的外周血样DNA,进行全外显子组测序(whole exome sequence,WES),用Sanger测序对候选变异进行家系验证。 结果 经trio-WES数据分析,筛选到与患儿临床表型相关的HECW2基因c.4505G>C(p.Gly1502Ala)变异,Sanger测序的结果与trio-WES一致,经双亲验证证实为新发变异。根据美国医学遗传学与基因组学(American College of Medical Genetics and Genomics,ACMG)指南对变异位点c.4505G>C(p.Gly1502Ala)进行致病性评估为可能致病性变异(PS2+PM2_Supporting+PP2+PP3_Moderate)。 结论 本研究患儿HECW2基因c.4505G>C(p.Gly1502Ala)杂合变异尚未报道,该发现为患者明确诊断提供了依据,且扩展了其致病变异谱,对患儿的确诊、遗传咨询及其父母的再生育指导具有重要的意义。 Objective To analyze the molecular genetic etiology of a patient with neurodevelopmental delay. Methods A 8-month-old female child who was admitted to Gansu Provincial Maternity and Child HealthCare Hospital on May 9, 2022 due to developmental delay and malnutrition was selected as the study subject.Clinical data of the child was collected, and genomic DNA was extracted from peripheral blood samples from the child and her parents. Whole exome sequencing(WES)was carried out, and candidate variants were verified by Sanger sequencing. Results After analyzing the data from trio WES, a variant of the HECW2 gene c. 4505G>C (p.Gly1502Ala) was identified that is related to the clinical phenotype of the patient. The results of Sanger sequencing were consistent with trio WES, and confirmed as a novel variant through parental verification. Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG), the c. 4505G>C(p.Gly1502Ala) variant was graded as likely pathogenic(PS2+ PM2_Supporting+ PP2+ PP3_Moderate). Conclusion The heterozygous variation of the HECW2 gene c. 4505G>C(p.Gly1502Ala) in this study is an unreported mutation.Our findings not only provide a clear diagnosis for this patient, but also expand their pathogenic spectrum. Above finding has facilitated definite diagnosis, genetic counseling for her family.
Genetic analysis of a child patient with neurodevelopmental delay caused byHECW2 gene variant
Objective To analyze the molecular genetic etiology of a patient with neurodevelopmental delay. Methods A 8-month-old female child who was admitted to Gansu Provincial Maternity and Child HealthCare Hospital on May 9, 2022 due to developmental delay and malnutrition was selected as the study subject.Clinical data of the child was collected, and genomic DNA was extracted from peripheral blood samples from the child and her parents. Whole exome sequencing(WES)was carried out, and candidate variants were verified by Sanger sequencing. Results After analyzing the data from trio WES, a variant of the HECW2 gene c. 4505G>C (p.Gly1502Ala) was identified that is related to the clinical phenotype of the patient. The results of Sanger sequencing were consistent with trio WES, and confirmed as a novel variant through parental verification. Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG), the c. 4505G>C(p.Gly1502Ala) variant was graded as likely pathogenic(PS2+ PM2_Supporting+ PP2+ PP3_Moderate). Conclusion The heterozygous variation of the HECW2 gene c. 4505G>C(p.Gly1502Ala) in this study is an unreported mutation.Our findings not only provide a clear diagnosis for this patient, but also expand their pathogenic spectrum. Above finding has facilitated definite diagnosis, genetic counseling for her family.

Neurodevelopmental delayHECW2 geneWhole exome sequencingGenetic variant

陈雪、马盼盼、田芯瑗、郑雷、张钏、郝胜菊、惠玲、周秉博

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甘肃省妇幼保健院,甘肃省中心医院医学遗传中心,甘肃省出生缺陷与罕见病临床研究中心,兰州 730050

神经发育迟滞 HECW2基因 全外显子测序 基因变异

甘肃省科技计划甘肃省科技计划甘肃省科技计划甘肃省妇幼保健院重大攻关项目(2021)

21JR7RA68022YF7FA09421JR1RA045

2024

国际遗传学杂志
中华医学会 哈尔滨医科大学

国际遗传学杂志

影响因子:0.175
ISSN:1673-4386
年,卷(期):2024.47(1)
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