已发表的467例软骨发育不全患者的综述：临床和突变谱。
Review of published 467 achondroplasia patients: clinical and mutational spectrum.
作者信息
Zhang XinZhong, Jiang Shan, Zhang Rui, Guo Siyi, Sheng Qiqi, Wang Kaili, Shan Yuanyuan, Liao Lin, Dong Jianjun
机构信息
Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Department of Endocrinology and Metabology, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Nephrology, Jinan, China.
出版信息
Orphanet J Rare Dis. 2024 Jan 27;19(1):29. doi: 10.1186/s13023-024-03031-1.
AIM
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.
CONCLUSION
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.
目的
软骨发育不全是导致儿童致命性和致残性生长发育障碍的最常见骨骼发育异常疾病，由成纤维细胞生长因子受体3型基因（FGFR3）突变引起。本研究旨在分析软骨发育不全的临床特征和基因突变情况，以准确判断患者是否患有软骨发育不全，并提高公众对该疾病的认识。
方法
以“Achondroplasias”或“Skeleton-Skin-Brain Syndrome”或“Skeleton Skin Brain Syndrome”或“ACH”以及“Receptor, Fibroblast Growth Factor, Type 3”或“FGFR3”为检索词，检索Pubmed、Cochrane图书馆、万方和知网数据库。
结果
最终纳入467例具有不同FGFR3突变的患者。在138例有性别信息的患者中，女性55例（55/138，40%），男性83例（83/138，60%）。在有家族史信息的患者中，47例（47/385，12%）有家族史，338例（338/385，88%）患者为散发病例。患者年龄从新生儿到36岁不等。其父亲的平均年龄为37±7岁（范围31 - 53岁）。患者来自12个国家和2个大洲，大多数为亚洲人（383/432，89%），其次是欧洲人（49/432，11%）。112例（112/112）患者存在身材矮小伴四肢短小，94例（94/112）患者有大头畸形异常，89例（89/112）患者有额部隆起，64例（64/112）患者有膝外翻，51例（51/112）患者有三叉手。最常见的突变是FGFR3基因的p.Gly380Arg，包含两种不同的碱基变化，即c.1138G＞A和c.1138G＞C。发现了10种罕见的致病突变，包括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和c.970_971insTCTCCT。
结论
软骨发育不全由FGFR3基因突变引起，c.1138G＞A是最常见的突变类型。本研究证明了分子基因检测对于早期发现身材矮小、三叉手、额部隆起、大头畸形和膝外翻青少年软骨发育不全的可行性。
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