两种罕见遗传病共病患儿2例的临床及遗传学特征分析  

Clinical and genetic characteristics analysis of two children with comorbidity of two rare genetic diseases

作　　者：甘玲[1] 梁瑞瑞 李月琴[1] 李梦春 李怡 赵世超 王丽君[1] 贾天明[1] 董燕[1] Gan Ling;Liang Ruirui;Li Yueqin;Li Mengchun;Li Yi;Zhao Shichao;Wang Lijun;Jia Tianming;Dong Yan(Department of Pediatric Neurology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第三附属医院小儿神经内科,郑州450052

出　　处：《中华医学遗传学杂志》2025年第1期34-40,共7页Chinese Journal of Medical Genetics

基　　金：河南省小儿脑损伤重点实验室既河南省儿科疾病临床医学研究中心联合开放课题(KFKT2021003);河南省科技攻关计划(242102311058)。

摘　　要：目的探讨2例同时诊断为两种罕见遗传病的患儿的临床及遗传学特征。方法选取2022年5月至2023年3月于郑州大学第三附属医院就诊的2例因两个基因同时发生变异导致两种罕见遗传病共病的患儿作为研究对象,总结其临床及遗传学特征。本研究通过了郑州大学第三附属医院医学伦理委员会的审查(批准号:2021-062-01)。结果患儿1为2岁4月龄男童,表现为特殊面容、发育落后、身材矮小、小头畸形、腭裂、隐睾、尿道下裂,伴有反复感染及免疫异常,全外显子组测序提示其同时携带KMT2D基因c.6595delT(p.Y2199Ifs*65)以及PIK3R1基因c.1892G>A(p.R631Q)新发杂合变异,诊断为Kabuki综合征和PI3Kδ相关免疫缺陷36型。患儿2为15岁女童,表现为癫痫、Albright遗传性骨营养不良症体型、身材矮小、长躯干、短四肢;实验室检查发现低血钙、高血磷、高甲状旁腺素。患儿有身材矮小家族史。全外显子组测序提示其同时携带GNAS基因c.2T>C(p.Met1?)杂合变异以及SHOX基因第2~6外显子缺失,诊断为假性甲状旁腺功能减退症和X-连锁特发性矮小。结论当遗传病的表型复杂且不能用一种基因变异完全解释或比预期严重时,须考虑两个以上的基因变异导致多种遗传病共病的可能性,并及时采取或补充相应的检测,必要时可对基因检测数据进行再分析,为临床确诊提供依据。ObjectiveTo explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously.MethodsTwo children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects.Clinical and genetic data of the two children were retrospectively analyzed.This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University(Ethic No.2021-062-01).ResultsChild 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism,developmental delay,short stature,microcephaly,cleft palate,cryptorchidism,hypospadias,recurrent infections and immunological abnormalities.Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT(p.Y2199Ifs*65)variant of the KMT2D gene and a heterozygous c.1892G>A(p.R631Q)variant of the PIK3R1 gene.This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36.Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy,Albright′s hereditary osteodystrophy,long body trunk,short limbs,hypocalcemia,hyperphosphatemia and hyperparathyroidism.The child also had a family history of short stature.Whole exome sequencing revealed that she had harbored a heterozygous c.2T>C(p.Met1?)variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene.The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature.ConclusionWhen the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant,multiple pathogenic variants should be considered,and this may lead to the diagnosis of co-morbid genetic diseases.To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of comorbid genetic diseases.

关 键 词：遗传病 共病 基因检测 临床表型 精准诊断 

分 类 号：R72[医药卫生—儿科]