一个PHEX基因新发变异导致的X-连锁低磷性佝偻病家系  

X-linked hypophosphatemic rickets caused by a de novo PHEX gene variation in a family

作　　者：张玉海[1] 张娴 方团育[1] 全会标[1] 陈开宁[1] 盛志峰[2,3] ZHANG Yuhai;ZHANG Xian;FANG Tuanyu;QUAN Huibiao;CHEN Kaining;SHENG Zhifeng(Deparment of Endocrinology,Hainan General Hospital,Haikou 570311;National Clinical Research Center for Metabolic Diseases,Hunan Provincial Key Laboratory of Metabolic Bone Diseases,epartment of Metabolism and Endocrinology,Second Xiangya Hospital,Central South University,Changsha 410011;Health Management Center,Second Xiangya Hospital,Central South University,Changsha 410011,China)

机构地区：[1]海南省人民医院内分泌科,海口570311 [2]国家代谢性疾病临床研究中心,代谢性骨病湖南省重点实验室,中南大学湘雅二医院代谢内分泌科,长沙410011 [3]中南大学湘雅二医院健康管理中心,长沙410011

出　　处：《中南大学学报（医学版）》2021年第6期658-665,共8页Journal of Central South University ：Medical Science

基　　金：海南省卫生健康行业科研项目(20A200160)。

摘　　要：X-连锁低磷性佝偻病(X-linked hypophosphatemicrickets,XLH)是最常见的遗传性佝偻病,主要由PHEX基因的失活变异引起,治疗起来较其他类型的佝偻病更复杂。海南省人民医院内分泌科2018年收治1个XLH家系。先证者,女,3岁6个月,汉族,因“双膝关节外翻、行走不稳”入院。患者表现为“O”型腿、手镯征、鸡胸及低血磷,骨骼X线检查结果提示佝偻病改变。父母非近亲结婚,家族中无人有类似疾病病史。提取患儿及其父母外周血DNA,采用PCR扩增患儿PHEX编码区的全部外显子及其侧翼序列,并通过一代测序验证其父母的变异位点。患儿PHEX基因13号内含子剪接区域上存在1个影响剪接的杂合变异(c.1482+5G>C),该变异已被人类基因突变数据库(human genemutationdatabase,HGMD)和ClinVar收录。此PHEX基因变异为新发变异,患儿父母均未发现该变异。本研究为患儿的遗传咨询提供了参考,并丰富了研究基因型与临床表现之间关系的临床资料。X-linked hypophosphatemic rickets(XLH)is caused by inactivating mutations in the PHEX gene and is the most common form of hereditary rickets.The treatment is more complicated compared with the general rickets.A family were admitted to the Department of Endocrinology,Hainan General Hospital in 2018.The proband was a 3-year-6-monthold female,Han nationality.She was admitted to hospitalization for bilateral knee valgus and walking instability.The patient’s parents were not in consanguineous marrige,and there was no similar medical history in the family.The patient presented with“O”leg,bracelet sign,chicken breast,and low blood phosphorus.Typical change of rickets also appeared in her X-ray examination.The DNAs of the peripheral blood were extracted from the patient and her parents.All coding exons and flanking regions of PHEX gene in the patient were amplified by PCR,and the mutant sites of the family members were testified by a generation sequencing.A heterozygous variation(c.1482+5G>C)affecting splicing outcome was detected at the splicing region of intron 13 of PHEX gene in the patient.The variation has been included in the human gene mutation database(HGMD).No variation was found in the proband’s parents,the PHEX gene in the patient was a de novo variation.Our research provided reference for the future genetic counseling for this patient and enriched the research data on the relationship between genotype and clinical manifestations.

关 键 词：X-连锁 低磷性佝偻病 PHEX 基因变异 

分 类 号：R725.9[医药卫生—儿科]