摘要
本研究收集2个汉族Okihiro综合征家系患者的临床表现,应用外显子组测序对2个家系的先证者进行检测,Sanger测序对家系成员进行基因型分析,以确定生物学发病机制,并为家系中的3个高危胎儿提供产前诊断。2个家系的患者表现出广泛的表型,尤其是家系1的先证者在胎儿期就发现超声异常(桡骨畸形、姿势异常、永存动脉干和室间隔缺损等心脏畸形),其余患者表现从严重表型(前臂严重缩短和变形、杜安异常、听力障碍),到不太明显的情况(仅有大鱼际发育不良、桡骨茎突较短小)。外显子组测序在2个家系的先证者中分别发现SALL4基因变异:c.844delC p(.Q282Kfs*8)和c.2210delG p(.G737Vfs*23),其中c.2210delG p(.G737Vfs*23)为新变异。家系验证发现患者成员均携带变异,正常成员中均未检测到。同时,3个高危胎儿中共检出1例正常基因型胎儿,2例携带杂合变异胎儿并终止妊娠。本研究通过外显子组测序和Sanger测序明确了2个Okihiro综合征家系的分子病理学原因,丰富了Okihiro综合征在围产期的临床表现和SALL4基因突变图谱,同时为3个高危胎儿提供产前诊断,有效降低生育患儿的风险。
In the present study,clinical manifestations of two Chinese Okihiro syndrome families were analyzed,and genetic detections were performed on the two probands by exome sequencing and verified by Sanger sequencing for family members to determine the biological pathogenesis.Prenatal diagnoses were provided for three high‐risk fetuses.The affected members exhibited a wildly spectrum of phenotypes,including ultrasound abnormalities of skeletal system(radius deformity and abnormal posture),and cardiac system(persistent common arterial trunk and ventricular septal defect)in the prenatal period of family 1,the severe phenotypes(grossly shortened and deformed forearm,Duane′s anomaly and hearing loss),and the mild ones(usually only thenar dysplasia,or short radius styloid process).Two SALL4 variants,c.844delC p.(Q282Kfs*8)and c.2210delG p.(G737Vfs*23),have been identified respectively in two probands,and c.2210delG of SALL4 gene was unreported previously.The two variants were verified in all affected individuals,not in normal family members.Genotyping results of three fetuses indicated that one fetus was normal,and the two fetuses with heterozygous variation were affected.The two variants of SALL4 gene,c.844delC p.(Q282Kfs*8)and c.2210delG p.(G737Vfs*23),were the molecular pathological cause of Okihiro syndrome in the present study and enriched the spectrum of SALL4 variants.Our study provides accurate prenatal genetic diagnosis for the two families to avoid the birth of affected children.
作者
白莹
吴庆华
李福祯
孙玥
王莉
焦智慧
孔祥东
Bai Ying;Wu Qinghua;Li Fuzhen;Sun Yue;Wang Li;Jiao Zhihui;Kong Xiangdong(Genetic and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Ophthalmology Department,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)
出处
《中华医学杂志》
CAS
CSCD
北大核心
2023年第26期2006-2010,共5页
National Medical Journal of China
基金
河南省医学科技攻关计划(201702003)
