CNNM2基因杂合突变致低镁血症-癫痫-精神发育迟滞一例报告并文献复习

Hypomagnesemia,seizures,mental retardation caused by heterozygous mutation of CNNM2:a case report and literatures review

目的分析1例CNNM2基因杂合突变致低镁血症-癫痫-精神发育迟滞(HOMGSMR1)[MIM:616418]患儿的临床特点,探讨基因型与表型之间的关联。方法随访并回顾性分析浏阳市妇幼保健院诊治的1例CNNM2基因杂合突变致HOMGSMR1病例临床特点,通过家系全外显子测序,对原始数据进行生物信息学分析,查阅人类孟德尔遗传(OMIM)、ClinVar、gnomAD、GeneReviews、Pubmed、中国知网等数据库及文献资料,采用美国医学遗传学和基因组学学会(ACMG)指南对锁定CNNM2基因杂合缺失变异进行评级。结果患儿,男,3个月18 d,母亲孕1产1,反复抽搐10余天,多次查血镁均低于正常水平,波动于0.51~0.55 mmol/L,予以口服"奥卡西平""硫酸镁"治疗后抽搐好转,血镁浓度有提高,但仍低于正常,最高为0.61 mmol/L。家系全外显子测序结果显示:患儿携带CNNM2基因外显子区域(c.838843delATGGCCp.M280A281del)杂合缺失突变,该变异未在其父母体内检出,提示为新发突变,大规模人群频率数据库gnomAD未收录该变异,未见文献报道该变异,根据ACMG指南,评级为疑似致病变异。该基因的致病变异可导致常染色体显性HOMGSMR1,符合遗传模式。结论CNNM2基因c.838843delATGGCC(p.M280A281del)是该患儿的疑似致病性变异,基因型与表型相符、杂合突变符合遗传模式,常染色体显性遗传是该患儿临床表现的分子病因,为未报道过的新突变。

Objective To analyze the clinical characteristics of a case of CNNM2 gene heterozygous mutation causing hypomagnesemia epilepsy mental retardation(HOMGSMR1)[MIM:616418]in a child,and explore the association between genotype and phenotype.Methods We followed up and retrospectively analyzed the clinical characteristics of a case of HOMGSMR1 caused by CNNM2 gene heterozygous mutation treated at Maternal and Child Health Care Hospital of Liuyang.Through whole exome sequencing of the family and bioinformatics analysis of the original data,we consulted databases and literature materials such as Online Mendelian Inheritance in Man(OMIM),ClinVar,gnomAD,GeneReviews,Pubmed,and China National Knowledge Infrastructure(CNKI),The American College of Medical Genetics and Genomics(ACMG)guidelines were used to rate heterozygous deletion mutations in the locked CNNM2 gene.Results Patient,male,3 months and 18 days old,mother gave birth to 1 child with 1 pregnancy,recurrent convulsions for more than 10 days,and multiple tests showed that blood magnesium levels were below normal,fluctuating between 0.51-0.55 mmol/L;After oral administration of"oxcarbazepine"and"magnesium sulfate",convulsions improved and blood magnesium concentration increased,but remained below normal,with the highest being 0.61 mmol/L.The sequencing results of the whole exome display of the family showed that the child carried a heterozygous deletion mutation in the exon region of the CNNM2 gene(c.838_843delATGGCCp.M280-A281del),which was not detected in their parents,indicating a new mutation.The large-scale population frequency database gnomAD did not include this mutation,and no literature reported this mutation.According to the ACMG guidelines,it was rated as a suspected pathogenic variant.The pathogenic variation of this gene can lead to autosomal dominant HOMGSMR1,which was consistent with genetic patterns.Conclusions CNNM2 gene c.838_843delATGGCC(p.M280_A281del)is a suspected pathogenic variant in this patient,with genotype and phenotype matching and heterozygous mutations following genetic patterns.Autosomal dominant inheritance is the molecular cause of clinical manifestations in this patient,and it is an unreported novel mutation.