一例醛固酮合成酶缺乏症患儿的临床及基因变异分析  

Clinical and genetic analysis of an infant with Aldosterone synthase deficiency

作　　者：杨海花[1] 陈琼[1] 张璐 崔岩[1] 卫海燕[1] Yang Haihua;Chen Qiong;Zhang Lu;Cui Yan;Wei Haiyan(Children’s Hospital Affiliated to Zhengzhou University,Henan Children’s Hospital,Zhengzhou Children’s Hospital,Henan Provincial Key Laboratory of Children’s Genetics and Metabolic Diseases,Zhengzhou,Henan 450000,China;WeHealth Biomedical Technology Co.,Ltd.,Shanghai 201315,China)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院,郑州儿童医院,河南省儿童遗传代谢性疾病重点实验室,450000 [2]上海韦翰斯生物医药科技有限公司,201315

出　　处：《中华医学遗传学杂志》2021年第9期865-868,共4页Chinese Journal of Medical Genetics

基　　金：河南省高等学校重点科研项目计划(19A320069)。

摘　　要：目的分析1例醛固酮合成酶缺乏症患儿的临床特点及致病基因,为遗传咨询和产前诊断提供依据。方法收集1例2个月1天的醛固酮合成酶缺乏症患儿的临床资料,应用高通量测序技术对患儿全外显子筛查,采用Sanger测序方法对家系进行验证和遗传分析。结果患儿男,身长54 cm(-2.1 SD),体重3.9 kg(-2.8 SD),反复呕吐、吃奶差、精神差、体重增长缓慢,血钠120 mmol/L、血钾6.84 mmol/L,促肾上腺皮质激素5.01 pg/mL、皮质醇21.95μg/dL、17羟孕酮1.314 ng/mL、雄烯二酮<0.3 ng/mL、睾酮2.09 ng/mL,均正常,肾素活性14.97,升高,醛固酮6.8 pg/mL,降低,测序结果显示患儿存在CYP11B2复合杂合变异,其中第8外显子c.1334T>G(p.Phe445Cys)杂合变异遗传自父亲,第6外显子c.1121G>A(p.Arg374Gln)杂合变异遗传自母亲,均为未报道过的新变异。结论CYP11B2基因c.1334T>G和c.1121G>A变异可能是患儿的致病原因。Objective To analyze the clinical characteristics and genetic variants in a two-month-and-one-day male infant with aldosterone synthase deficiency.Methods Clinical data of the child was collected.Whole exome sequencing was carried out by next generation sequencing(NGS).Candidate variants were verified by Sanger sequencing.Results The infant had measured 54 cm(-2.1 SD)in length and 3.9 kg(-2.8 SD)in weight,and featured recurrent vomiting,poor feeding,apathetic appearance and failure to thrive.Blood electrolyte testing showed low sodium and increased potassium.Serum cortisol,adrenocorticotrophic hormone,17-α-hydroxyl progesterone,androstenedione,and testosterone were all within the normal ranges.The plasma renin activity activity was increased,and plasma aldosterone level was low.NGS revealed that the infant has harbored compound heterozygous variants of the CYP11B2 gene,namely c.1334T>G(p.Phe445Cys)inherited from his father and c.1121G>A(p.Arg374Gln)inherited from his mother.Neither variant was reported previously,and both were predicted to be deleterious for the function of the protein product.Conclusion The compound heterozygous variants of c.1334T>G(p.Phe445Cys)and c.1121G>A(p.Arg374Gln)of the CYP11B2 gene probably underlay the disease in this patient.

关 键 词：CYP11B2基因 醛固酮合成酶 复合杂合变异 

分 类 号：R725.8[医药卫生—儿科]