耳-腭-指综合征1型新生儿围产期临床特征和遗传特点分析  

Analysis of perinatal clinical features and genetic characteristics of a neonate with otopalatodigital syndrome type 1

作　　者：赵旭亮 田瑞霞[2] 李旭 贾建安 俞敏 朱复希[1] ZHAO Xuliang;TIAN Ruixia;LI Xu;JIA Jian'an;YU Min;ZHU Fuxi(Reproductive Medicine Center,Department of Obstetrics,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui,China;Department of Obstetrics and Gynecology,the No.901 Hospital of the Joint Service of the People's Liberation Army,Hefei 230031,Anhui,China;Magnetic Resonance Imaging Room,Anhui Provincial Children's Hospital,Hefei 230051,Anhui,China;Department of Clinical Laboratory,the No.901 Hospital of the Joint Service of the People's Liberation Army,Hefei 230031,Anhui,China)

机构地区：[1]安徽医科大学第一附属医院妇产科生殖医学中心,安徽合肥230022 [2]中国人民解放军联勤保障部队第901医院妇产科,安徽合肥230031 [3]安徽省儿童医院磁共振室,安徽合肥230051 [4]中国人民解放军联勤保障部队第901医院检验科,安徽合肥230031

出　　处：《检验医学》2022年第8期710-714,共5页Laboratory Medicine

基　　金：安徽省自然科学基金资助项目(1908085J28)。

摘　　要：目的对1例耳-腭-指综合征1型(OPD1)患儿围产期的临床特征和遗传特点进行分析,提高临床对此类罕见病的认识。方法收集1例OPD1患儿的临床资料,对患儿及其父母进行全外显子家系测序(Trio-WES)。采用Sanger测序对变异位点进行验证。采用生物信息学分析评估变异位点的危害性。结合文献对细丝蛋白A(FLNA)基因热点变异患儿的临床特征进行回顾性分析。结果产前超声提示患儿小下颌、鼻梁塌陷、脊椎排列异常、双足第2趾长,出生后患儿具有眼距较宽、眼睑裂倾斜、鼻梁塌陷、下颌后缩、耳位低且右耳可见副耳、双足第2趾明显长于其余4趾的体貌特征。基因检测结果提示患儿FLNA基因发生杂合变异(c.620C>T/p.Pro207Leu),患儿母亲存在该位点变异,父亲基因型为野生型。文献回顾分析结果显示,FLNA基因c.620C>T/p.Pro207Leu是导致OPD1的热点变异,携带该变异的患者可表现为眼距宽、眼睑裂倾斜、小下颌、腭裂、不同类型的指(趾)骨畸形、听力下降等临床特征。结论FLNA基因c.620C>T/p.Pro207Leu变异可导致OPD1的发生。结合家系资料分析、产前超声检查和家系基因分析是诊断耳-腭-指谱系障碍(OPDSD)并进一步分型的有效方法。Objective To investigate the perinatal clinical features and genetic characteristics of a neonate with otopalatodigital syndrome type 1(OPD1),and to improve the clinical understanding of such rare diseases.Methods The clinical data of a neonate with OPD1 was collected.The genes of the neonate and his parents were determined by trio-whole exome sequencing(Trio-WES).Variation sites were verified by Sanger sequencing.The biohazard of gene mutation was analyzed by relevant prediction software.The clinical features of the neonate with filamin A(FLNA)gene hot spot mutation were analyzed retrospectively.Results Prenatal ultrasound showed that the fetal had clinical manifestations such as micrognathia,nasal collapse,abnormal spinal alignment and the length of the second toes of both feet.After birth,the case had a special appearance of ocular hypertelorism,collapsed nasal bridge and wide nasal root,small mandible and backward retraction,low ear position and accessory ear.The results of gene test showed that the FLNA gene had heterozygous mutation(c.620C>T/p.Pro207Leu),his mother carried the same variant,and his father has wild type.Literature reviewing showed that FLNA gene c.620C>T/p.Pro207Leu was the hot spot variant causing to OPD1.The high frequency phenotypes of the mutation was ocular hypertelorism,eyelid cleft,micrognathia,cleft palate,different types of finger(toe)deformity and hearing loss.Conclusions OPD1 is caused by FLNA gene hot spot variant c.620C>T/p.Pro207Leu.The combination of family datum analysis,prenatal ultrasound and family gene analysis is an effective method for the diagnosis and further typing of otopalatodigital spectrum disorder(OPDSD).

关 键 词：细丝蛋白A 耳-腭-指综合征1型 耳-腭-指谱系障碍 

分 类 号：R446.1[医药卫生—诊断学]