Prinster C, Carrera P, Del Maschio M, Weber G, Maghnie M, Vigone M C, Mora S, Tonini G, Rigon F, Beluffi G, Severi F, Chiumello G, Ferrari M
Department of Pediatrics, Scientific Institute H San Raffaele, University of Milan, Italy.
Am J Med Genet. 1998 Jan 6;75(1):109-12. doi: 10.1002/(sici)1096-8628(19980106)75:1<109::aid-ajmg22>3.0.co;2-p.
Hypochondroplasia is an autosomal dominant skeletal dysplasia characterized by disproportionate short stature. A mutation (N540K) in the fibroblast growth factor receptor 3 (FGFR3) gene was described in some patients with this condition. The aims of the study were to identify the frequency of the FGFR3 gene mutation, to define the salient clinical and radiological abnormalities of the affected subjects, and to verify the contribution of molecular findings to the clinical and radiological definition of hypochondroplasia. Based on the most common radiological criteria, we selected 18 patients with a phenotype compatible with hypochondroplasia. Height, sitting height, and cranial circumference were measured in all patients. Radiographs of the lumbar spine, left leg, pelvis, and left hand were also obtained. The presence of the N540K mutation was verified by restriction enzyme digestions. Half of our patients carried the N540K mutation. Although similar in phenotype to the patients without the mutation, they showed in addition relative macrocephaly. The association of the unchanged/narrow interpedicular distance with the fibula longer than the tibia was more common in patients with gene mutation. Although we did not find a firm correlation between genotype and phenotype, in our study the N540K mutation was most often associated with disproportionate short stature, macrocephaly, and with radiological findings of unchanged/narrow interpedicular distance and fibula longer than tibia.
软骨发育不全是一种常染色体显性遗传性骨骼发育不良，其特征为身材不成比例地矮小。在一些患有这种疾病的患者中，已发现成纤维细胞生长因子受体3（FGFR3）基因存在一种突变（N540K）。本研究的目的是确定FGFR3基因突变的频率，明确受影响受试者的主要临床和放射学异常，并验证分子检测结果对软骨发育不全临床和放射学定义的作用。基于最常用的放射学标准，我们选取了18例表型符合软骨发育不全的患者。测量了所有患者的身高、坐高和头围。还获取了腰椎、左腿、骨盆和左手的X光片。通过限制性酶切验证N540K突变的存在。我们的患者中有一半携带N540K突变。尽管他们的表型与未发生突变的患者相似，但除此之外还表现出相对头大。椎弓根间距不变/变窄且腓骨长于胫骨的情况在基因突变患者中更为常见。尽管我们未发现基因型与表型之间存在确切关联，但在我们的研究中，N540K突变最常与身材不成比例矮小、头大以及椎弓根间距不变/变窄和腓骨长于胫骨的放射学表现相关。
