染色体10q24.31片段重复导致先天性缺指/缺趾畸形的一个家系致病机理分析

doi:10.16288/j.yczz.19-125

遗传 ›› 2019, Vol. 41 ›› Issue (8): 716-724.doi: 10.16288/j.yczz.19-125

染色体10q24.31片段重复导致先天性缺指/缺趾畸形的一个家系致病机理分析

张秀泉^1,²,王建³,熊符³,吕伟标¹,周远青¹,杨少民⁴,张玉婷²,田小燕²,连蔚²,徐湘民³

^1. 南方医科大学顺德医院检验科,生殖遗传研究室,佛山 528300
^2. 南方医科大学顺德医院妇产科,佛山 528300
^3. 南方医科大学医学遗传学教研室,广州 510515
^4. 南方医科大学顺德医院放射科,佛山 528300

收稿日期:2019-05-07 修回日期:2019-07-18 出版日期:2019-08-20 发布日期:2019-07-09
作者简介:张秀泉,博士,教授,研究方向: 妇产科生殖遗传。E-mail:zhangxiuquan@yahoo.com
基金资助:
南方医科大学顺德医院临床研究基金项目资助(CRSP2019009)

Congenital ectrodactyly caused by chromosome 10q24.31 duplication and its pathogenetic analysis

Zhang Xiuquan^1,²,Wang Jian³,Xiong Fu³,Lv Weibiao¹,Zhou Yuanqing¹,Yang Shaomin⁴,Zhang Yuting²,Tian Xiaoyan²,Lian Wei²,Xu Xiangmin³

^1. Department of General Laboratories, Reproductive Genetic Research Laboratory, Shunde Hospital, Southern Medical University, Foshan 528300, China
^2. Department of Obstetrics and Gynecology, Shunde Hospital, Southern Medical University, Foshan 528300, China
^3. Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
^4. Department of Radiology, Shunde Hospital, Southern Medical University, Foshan 528300, China

Received:2019-05-07 Revised:2019-07-18 Online:2019-08-20 Published:2019-07-09
Supported by:
Supported by Clinical Research Fund, Shunde Hospital of Southern Medical University(CRSP2019009)

摘要/Abstract

摘要：

先天性缺指/缺趾畸形表现为手足指/趾骨发育不全等症状,会严重影响患者生活中的精细操作及心理健康。本研究对一个患有先天性缺指/缺趾畸形家系进行了基因变异检测,分析总结了该疾病分型与基因变异之间的关联关系,并探讨了对此类疾病患者开展遗传咨询及基因诊断的策略。首先,采用临床体检及四肢X线检查的方式,对患者表型进行分析。然后,应用D10S1709、D10S192、D10S597、D10S1693和D10S587等5个位点对外周血DNA进行了单倍型分析,并利用Array-CGH检测基因重复片段。最后,通过基于家系调查和基因分析探讨先天性手足裂畸形的致病原因。研究结果显示,先证者为典型的先天性手足裂畸形,表现为双侧食、中指缺失,拇指短,左手无名指畸形与缺失中指的皮肤相连成蹼状;双足正中裂开至足中部,第2和3趾缺失,第4和5趾融合。家系中其他患者表型变异较大。其外周血基因单倍型分析表现为染色体10q24.31-10q24.32区域有一个至少610 kb的重复,Array-CGH分析结果为10q24.31(102 832 650~103 511 083)×3。对先证者及其弟弟和父母进行单倍型分析,确认该家系的致病基因为10q24.31-10q24.32基因重复,单倍型165-251-289-219-102为该病的等位基因。研究结果提示,该家系缺指/缺趾畸形乃由于染色体10q24.31 (102 832 650~103 511 083)×3引起,其单倍型165-251-289-219-102可作为检测10q24.31-10q24.32等位基因的疾病标志物。

关键词: 先天性手足裂畸形, 微阵列比较基因组杂交技术, 单体型基因分析, 遗传咨询

Abstract:

In order to investigate the genetic variations and the clinical manifestations of a range of congenital ectrodactyly family and to summarize the split hand/foot malformation (SHFM) types and their related pathogenic genes, we conducted phenotypic analyses of patient’s limbs by physical and X-ray examination. The haplotypes were analyzed by using the extracted genes from peripheral blood on D10S1709, D10S192, D10S597, D10S1693 and D10S587 loci, and the mutation duplication loci were confirmed by Array-CGH detection. The pathogenic factors and inheritance pattern of SHFM were analyzed based on family investigation and gene analysis. Results demonstrate the proband’s phenotype is typically of a congenital SHFM which is manifested by missing bilateral index and middle fingers, short bilateral thumbs, deformed left ring finger with webbing of the skin missing at the middle finger; bilateral big toe with the second and the third toe missing, fourth and fifth toe fusion leading to a deformed toe separated from the first toe by the middle of the foot. The haplotype analyses show that there is a repeat of at least 610 kb in chromosome 10q24.31-10q24.32 region. Array-CGH analysis shows 10q24.31 (102 832 650-103 511 083) ×3. Our results demonstrate that the pathogenic gene variation of ectrodactyly in this family is due to duplication of 10q24.31 (102 832 650~103 511 083). The haplotype 165-251-289-219-102 can be used as a disease marker for detecting 10q24.31~10q24.32 allele for SHFM.

Key words: congenital ectrodactyly, array-CGH, haplotype analysis, genetic counseling

张秀泉,王建,熊符,吕伟标,周远青,杨少民,张玉婷,田小燕,连蔚,徐湘民. 染色体10q24.31片段重复导致先天性缺指/缺趾畸形的一个家系致病机理分析[J]. 遗传, 2019, 41(8): 716-724.

Zhang Xiuquan,Wang Jian,Xiong Fu,Lv Weibiao,Zhou Yuanqing,Yang Shaomin,Zhang Yuting,Tian Xiaoyan,Lian Wei,Xu Xiangmin. Congenital ectrodactyly caused by chromosome 10q24.31 duplication and its pathogenetic analysis[J]. Hereditas(Beijing), 2019, 41(8): 716-724.

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染色体10q24.31片段重复导致先天性缺指/缺趾畸形的一个家系致病机理分析

Congenital ectrodactyly caused by chromosome 10q24.31 duplication and its pathogenetic analysis

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