Abstract：
OBJECTIVE: To explore the clinical and genetic characteristics of three children with Hyperekplexia.
METHODS: Three children who were diagnosed with Hyperekplexia at the Third Affiliated Hospital of Zhengzhou University between June 2018 and March 2020 were selected as the study subjects. Clinical data of the three children were collected. All children were subjected to whole exome sequencing. Pathogenicity of candidate variants were verified by Sanger sequencing and bioinformatic analysis.
RESULTS: The three children were all males, and had presented exaggerated startle reflexes and generalized stiffness in response to unexpected auditory or tactile stimulation, or had frequent traumatic falls following exaggerated startle. All children had shown positive nose-tapping reflex, though EEG and cranial MRI exams were all negative. Whole exome sequencing revealed that two children had harbored homozygous variants of the GLRB gene, of which the c.1017_c.1018insAG (p.G340Rfs*14) was unreported previously. The third child had harbored compound heterozygous variants of the GLRA1 gene, among which the c.1262T>A (p.IIe421Asn) variant showed an unreported autosomal recessive inheritance. All children had responded well to clonazepam treatment.
CONCLUSIONS: Patients with Hyperekplexia have typical clinical manifestations. Early clinical identification and genetic analysis can facilitate their diagnosis.
METHODS: Three children who were diagnosed with Hyperekplexia at the Third Affiliated Hospital of Zhengzhou University between June 2018 and March 2020 were selected as the study subjects. Clinical data of the three children were collected. All children were subjected to whole exome sequencing. Pathogenicity of candidate variants were verified by Sanger sequencing and bioinformatic analysis.
RESULTS: The three children were all males, and had presented exaggerated startle reflexes and generalized stiffness in response to unexpected auditory or tactile stimulation, or had frequent traumatic falls following exaggerated startle. All children had shown positive nose-tapping reflex, though EEG and cranial MRI exams were all negative. Whole exome sequencing revealed that two children had harbored homozygous variants of the GLRB gene, of which the c.1017_c.1018insAG (p.G340Rfs*14) was unreported previously. The third child had harbored compound heterozygous variants of the GLRA1 gene, among which the c.1262T>A (p.IIe421Asn) variant showed an unreported autosomal recessive inheritance. All children had responded well to clonazepam treatment.
CONCLUSIONS: Patients with Hyperekplexia have typical clinical manifestations. Early clinical identification and genetic analysis can facilitate their diagnosis.
摘要：
目的：探讨3例腰腿痛患儿的临床及遗传特点。
方法：选择2018年6月至2020年3月在郑州大学第三附属医院确诊为中风的3例患儿作为研究对象。收集3例患儿的临床资料。对所有儿童进行全外显子组测序。通过Sanger测序和生物信息学分析验证候选变异体的致病性。
结果：三个孩子都是男性，并在意外的听觉或触觉刺激下表现出夸张的惊吓反射和广义的僵硬，或者在夸张的惊吓之后经常有创伤性的跌倒。所有儿童都表现出积极的鼻子敲击反射，尽管脑电图和头颅MRI检查均为阴性。全外显子组测序显示，两个孩子携带GLRB基因的纯合变体，其中c.1017_c.1018insAG（p。G340Rfs*14）以前未报告。第三个孩子拥有GLRA1基因的复合杂合变体，其中c.1262T>A（p。IIe421Asn）变体显示出未报告的常染色体隐性遗传。所有儿童对氯硝西泮治疗反应良好。
结论：腰痛患者有典型的临床表现。早期临床鉴定和遗传分析可以促进其诊断。
方法：选择2018年6月至2020年3月在郑州大学第三附属医院确诊为中风的3例患儿作为研究对象。收集3例患儿的临床资料。对所有儿童进行全外显子组测序。通过Sanger测序和生物信息学分析验证候选变异体的致病性。
结果：三个孩子都是男性，并在意外的听觉或触觉刺激下表现出夸张的惊吓反射和广义的僵硬，或者在夸张的惊吓之后经常有创伤性的跌倒。所有儿童都表现出积极的鼻子敲击反射，尽管脑电图和头颅MRI检查均为阴性。全外显子组测序显示，两个孩子携带GLRB基因的纯合变体，其中c.1017_c.1018insAG（p。G340Rfs*14）以前未报告。第三个孩子拥有GLRA1基因的复合杂合变体，其中c.1262T>A（p。IIe421Asn）变体显示出未报告的常染色体隐性遗传。所有儿童对氯硝西泮治疗反应良好。
结论：腰痛患者有典型的临床表现。早期临床鉴定和遗传分析可以促进其诊断。
