软骨发育不全与软骨发育低下家系的FGFR3基因突变分析

临床儿科杂志 ›› 2014, Vol. 32 ›› Issue (4): 384-387.

软骨发育不全与软骨发育低下家系的FGFR3基因突变分析

李琳迪^1,2, 蓝丹^1,2, 杨湖^1,2, 许田田¹, 李琼艳¹, 高宗燕^1,2

1. 广西医科大学第一附属医院儿科（广西南宁　530021）；2. 广西医科大学生物靶向诊治研究中心（广西南宁　530021）

收稿日期:2013-11-09 出版日期:2014-04-15 发布日期:2014-04-15

FGFR3 gene mutation analysis of achondroplasia and hypochondroplasia families　

LI Lindi^1,2, LAN Dan^1,2, YANG Hu^1,2, XU Tiantian¹, LI Qiongyan¹, GAO Zongyan^1,2

(1.Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China; 2.Biological Targeting Diagnosis & Research Center of Guangxi Medical University, Nanning 530021, Guangxi, China)

Received:2013-11-09 Online:2014-04-15 Published:2014-04-15

摘要/Abstract

摘要：

　目的　了解临床诊断为软骨发育异常类疾病患儿及其家系成员的成纤维细胞生长因子受体3（FGFR3）基因突变情况。方法　应用聚合酶链式反应（PCR）和DNA测序技术分析7例患儿及其家系成员的FGFR3基因突变热点分布区域第10外显子以及第13外显子的序列。结果　4例患儿存在FGFR3基因第10外显子c.1138G>A（p.Gly380Arg）杂合突变，确诊为软骨发育不全（ACH），其父母未见突变。1例症状较轻微的患儿及其有同样表型的母亲存在FGFR3基因第13外显子c.1620C>A（p.Asn540Lys）杂合突变，确诊为软骨发育低下（HCH）。2例患儿未发现以上两个位点的突变。结论　检测FGFR3基因第10、第13外显子可诊断大部分ACH或HCH病例，但少数患儿尚有必要检测FGFR3基因其他区域及其他相关基因以明确诊断。

Abstract: 　Objective　To screen the sequence of fibroblast growth factor receptor 3 (FGFR3) genes in children with dyschondroplasia and their family members for searching the mutations. Methods The sequence of exon 10 and exon 13 in mutation hot spot region of FGFR3 gene in seven families was analyzed using polymerase chain reaction (PCR) and DNA sequencing technology. Results The c.1138G>A missense mutation in exon 10 was found in 4 probands who were diagnosed as achondroplasia (ACH), while this mutation was absent in their parents. The c.1620C>A missense mutation in exon 13 was found in one girl and her mother who both were diagnosed as hypochondroplasia (HCH) with mild symptoms. Neither mutation mentioned above was found in the other two probands. Conclusions Through detecting the mutation in exon 10, exon 13 of FGFR3 gene, most patients of ACH or HCH can be finally diagnosed. However, it is necessary to perform the mutation screening on the other zones of FGFR3 gene and on other related genes for a few cases.

李琳迪, 蓝丹, 杨湖, 许田田, 李琼艳, 高宗燕. 软骨发育不全与软骨发育低下家系的FGFR3基因突变分析[J]. 临床儿科杂志, 2014, 32(4): 384-387.

LI Lindi,LAN Dan,YANG Hu,XU Tiantian,LI Qiongyan,GAO Zongyan,. FGFR3 gene mutation analysis of achondroplasia and hypochondroplasia families　[J]. , 2014, 32(4): 384-387.

参考文献

[1] Baujat G，Legeai-Mallet L，Finidori G，et al. Achondroplasia [J]. Best Pract Res Clin Rheumatol，2008，22(1)：3-18.
[2] Richette P，Bardin T，Stheneur C. Achondroplasia：from genotype to phenotype [J]. Joint Bone Spine，2008，75(2)：125-130.
[3] Shiang R，Thompson LM，Zhu YZ，et al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism，achondroplasia [J]. Cell，1994，78(2)：335-342.
[4] Rousseau F，Bonaventure J，Legeai-Mallet L，et al. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia [J]. Nature，1994，371(6494)：252-254.
[5] Bellus GA，Spector EB，Speiser PW，et al. Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype [J]. Am J Hum Genet，2000，67(6)：1411-1421.
[6] 张明，赵文双，高智文. FGFR3突变与软骨发育不全的研究进展 [J]. 中国优生与遗传杂志，2010，18(5)：1-2.
[7] Bellus GA，Hefferon TW，Ortiz de Luna RI，et al. Achondroplasia is defined by recurrent G380R mutations of FGFR3 [J]. Am J Hum Genet，1995，56(2)：368-373.
[8] 张晔，喻唯民，沈明，等. FGFR3基因突变分析鉴别软骨发育不全及类似遗传性侏儒 [J]. 中华医学遗传学杂志，2000，17(4)：252-255.
[9] Superti-Furga A，Eich G，Bucher HU，et al. A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia [J]. Eur J Pediatr，1995，154(3)：215-219.
[10] Ikegawa S，Fukushima Y，Isomura M，et al. Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients [J]. Hum Genet，1995，96(3)：309-311.
[11] 朱斌，董秋明，黄兴华，等. 一个软骨发育不全家系成纤维细胞生长因子受体3基因突变分析 [J]. 中华医学遗传学杂志，2003，20(5)，373-375.
[12] Fryns JP，Kleczkowska A，Verresen H，et al. Germinal mosaicism in achondroplasia：a family with 3 affected siblings of normal parents [J]. Clin Genet，1983，24(3)：156-158.
[13] Matsui Y，Yasui N，Kimura T，et al. Genotype phenotype correlation in achondroplasia and hypochondroplasia [J]. J Bone Joint Surg Br，1998，80(6)：1052-1056.
[14] Grigelioniené G，Ekl?f O，Laurencikas E，et al. Asn540Lys mutation in fibroblast growth factor receptor 3 and phenotype in hypochondroplasia [J]. Acta Paediatr，2000，89(9)：1072-1076.
[15] Song SH，Balce GC，Agashe MV，et al. New proposed clinico-radiologic and molecular criteria in hypochondroplasia：FGFR 3 gene mutations are not the only cause of hypochondroplasia [J]. Am J Med Genet A，2012，158A(10)：2456-2462.
[16] Wang H，Sun Y，Wu W，et al. A novel missense mutation of FGFR3 in a Chinese female and her fetus with Hypochondroplasia by next-generation sequencing [J]. Clin Chim Acta，2013，423(1)：62-65.