PDF(Pubmed)
Abstract：
OBJECTIVE: Achondroplasia is the most common of the skeletal dysplasias that cause fatal and disabling growth and developmental disorders in children, and is caused by a mutation in the fibroblast growth factor receptor, type 3 gene(FGFR3). This study aims to analyse the clinical characteristics and gene mutations of ACH to accurately determine whether a patient has ACH and to raise public awareness of the disease.
METHODS: The database of Pubmed, Cochrane Library, Wanfang and CNKI were searched with terms of \"Achondroplasias\" or \"Skeleton-Skin-Brain Syndrome\" or \"Skeleton Skin Brain Syndrome\" or \"ACH\" and \"Receptor, Fibroblast Growth Factor, Type 3\" or \"FGFR3\".
RESULTS: Finally, four hundred and sixty-seven patients with different FGFR3 mutations were enrolled. Of the 138 patients with available gender information, 55(55/138, 40%) were female and 83(83/138, 60%) were male. Among the patients with available family history, 47(47/385, 12%) had a family history and 338(338/385, 88%) patients were sporadic. The age of the patients ranged from newborn babies to 36 years old. The mean age of their fathers was 37 ± 7 years (range 31-53 years). Patients came from 12 countries and 2 continents, with the majority being Asian (383/432, 89%), followed by European (49/432, 11%). Short stature with shortened arms and legs was found in 112(112/112) patients, the abnormalities of macrocephaly in 94(94/112) patients, frontal bossing in 89(89/112) patients, genu valgum in 64(64/112) patients and trident hand were found in 51(51/112) patients. The most common mutation was p.Gly380Arg of the FGFR3 gene, which contained two different base changes, c.1138G > A and c.1138G > C. Ten rare pathogenic mutations were found, including c.831A > C, c.1031C > G, c.1043C > G, c.375G > T, c.1133A > G, c.1130T > G, c.833A > G, c.649A > T, c.1180A > T and c.970_971insTCTCCT.
CONCLUSIONS: ACH was caused by FGFR3 gene mutation, and c.1138G > A was the most common mutation type. This study demonstrates the feasibility of molecular genetic testing for the early detection of ACH in adolescents with short stature, trident hand, frontal bossing, macrocephaly and genu valgum.
METHODS: The database of Pubmed, Cochrane Library, Wanfang and CNKI were searched with terms of \"Achondroplasias\" or \"Skeleton-Skin-Brain Syndrome\" or \"Skeleton Skin Brain Syndrome\" or \"ACH\" and \"Receptor, Fibroblast Growth Factor, Type 3\" or \"FGFR3\".
RESULTS: Finally, four hundred and sixty-seven patients with different FGFR3 mutations were enrolled. Of the 138 patients with available gender information, 55(55/138, 40%) were female and 83(83/138, 60%) were male. Among the patients with available family history, 47(47/385, 12%) had a family history and 338(338/385, 88%) patients were sporadic. The age of the patients ranged from newborn babies to 36 years old. The mean age of their fathers was 37 ± 7 years (range 31-53 years). Patients came from 12 countries and 2 continents, with the majority being Asian (383/432, 89%), followed by European (49/432, 11%). Short stature with shortened arms and legs was found in 112(112/112) patients, the abnormalities of macrocephaly in 94(94/112) patients, frontal bossing in 89(89/112) patients, genu valgum in 64(64/112) patients and trident hand were found in 51(51/112) patients. The most common mutation was p.Gly380Arg of the FGFR3 gene, which contained two different base changes, c.1138G > A and c.1138G > C. Ten rare pathogenic mutations were found, including c.831A > C, c.1031C > G, c.1043C > G, c.375G > T, c.1133A > G, c.1130T > G, c.833A > G, c.649A > T, c.1180A > T and c.970_971insTCTCCT.
CONCLUSIONS: ACH was caused by FGFR3 gene mutation, and c.1138G > A was the most common mutation type. This study demonstrates the feasibility of molecular genetic testing for the early detection of ACH in adolescents with short stature, trident hand, frontal bossing, macrocephaly and genu valgum.
摘要：
目的：软骨发育不良是导致儿童致命性和致残性生长和发育障碍的最常见的骨骼发育不良，是由成纤维细胞生长因子受体的突变引起的，3型基因(FGFR3)。这项研究旨在分析ACH的临床特征和基因突变，以准确确定患者是否患有ACH，并提高公众对该病的认识。
方法：Pubmed，科克伦图书馆,在万方和CNKI中搜索了“软骨发育不良”或“骨骼皮肤脑综合征”或“骨骼皮肤脑综合征”或“ACH”和“受体，成纤维细胞生长因子,键入3\"或\"FGFR3\"。
结果：最后，纳入了467例具有不同FGFR3突变的患者.在138名具有性别信息的患者中，55(55/138，40%)为女性，83(83/138，60%)为男性。在有家族史的患者中，47例（47/385，12%）患者有家族史，338例（338/385，88%）患者为散发性。患者的年龄从新生婴儿到36岁不等。他们父亲的平均年龄为37±7岁（范围31-53岁）。患者来自12个国家和2大洲，大多数是亚洲人(383/432，89%)，其次是欧洲（49/432，11%）。112例(112/112)患者身材矮小，胳膊和腿缩短，94例（94/112）患者的大头畸形，89（89/112）名患者的额叶隆起，64例（64/112）患者中发现了genuvalgum，51例（51/112）患者中发现了三叉戟手。最常见的突变是FGFR3基因的p.Gly380Arg，其中包含两个不同的基数变化，c.1138G>A和c.1138G>C。发现了十种罕见的致病性突变，包括c.831A>C，c.1031C>G，c.1043C>G，c.375G>T，c.113A>G，c.1130T>G，c.83A>G，c.649A>T，c.1180A>T和c.970_971insTCTCCT。
结论：ACH是由FGFR3基因突变引起的，和c.1138G>A是最常见的突变类型。这项研究证明了分子遗传检测对矮小青少年早期发现ACH的可行性，三叉戟手，额前带，大头畸形和genuvalgum。
方法：Pubmed，科克伦图书馆,在万方和CNKI中搜索了“软骨发育不良”或“骨骼皮肤脑综合征”或“骨骼皮肤脑综合征”或“ACH”和“受体，成纤维细胞生长因子,键入3\"或\"FGFR3\"。
结果：最后，纳入了467例具有不同FGFR3突变的患者.在138名具有性别信息的患者中，55(55/138，40%)为女性，83(83/138，60%)为男性。在有家族史的患者中，47例（47/385，12%）患者有家族史，338例（338/385，88%）患者为散发性。患者的年龄从新生婴儿到36岁不等。他们父亲的平均年龄为37±7岁（范围31-53岁）。患者来自12个国家和2大洲，大多数是亚洲人(383/432，89%)，其次是欧洲（49/432，11%）。112例(112/112)患者身材矮小，胳膊和腿缩短，94例（94/112）患者的大头畸形，89（89/112）名患者的额叶隆起，64例（64/112）患者中发现了genuvalgum，51例（51/112）患者中发现了三叉戟手。最常见的突变是FGFR3基因的p.Gly380Arg，其中包含两个不同的基数变化，c.1138G>A和c.1138G>C。发现了十种罕见的致病性突变，包括c.831A>C，c.1031C>G，c.1043C>G，c.375G>T，c.113A>G，c.1130T>G，c.83A>G，c.649A>T，c.1180A>T和c.970_971insTCTCCT。
结论：ACH是由FGFR3基因突变引起的，和c.1138G>A是最常见的突变类型。这项研究证明了分子遗传检测对矮小青少年早期发现ACH的可行性，三叉戟手，额前带，大头畸形和genuvalgum。
