目的:研究1例Ellis-vanCreveld综合征患者和2例Bardet-Biedl综合征患者的牙齿异常和分子病因,纤毛病的两个例子。
方法:临床检查,射线照相评估,整个外显子组测序,进行Sanger直接测序。
结果:患者1患有Ellis-vanCreveld综合征,伴有牙齿发育延迟或牙齿发育不全,和多个系带,该特征仅在纤毛基因突变的患者中发现。在EVC2中鉴定了新的纯合突变(c.703G>C;p.Ala235Pro)。患者2患有Bardet-Biedl综合征,在BBS7中具有纯合移码突变(c.389_390delAC;p.Asn130ThrfsTer4)。患者3患有Bardet-Biedl综合征,在BBS7中携带杂合突变(c.389_390delAC;p.Asn130ThrfsTer4),在BBS2中携带纯合突变(c.209G>A;p.Ser70Asn)。她的临床发现包括全球发育迟缓,不成比例的身材矮小,近视,视网膜色素变性,肥胖,宫腔积脓伴有阴道闭锁,双侧肾积水伴肾盂输尿管连接部梗阻,双侧膝外翻,后轴多指脚,又小又细的指甲和脚趾甲,牙齿发育不全,microdontia,牛磺酸症,牙本质形成受损。
结论:在我们的患者中发现的EVC2、BBS2和BBS7突变与包括牙齿发育不全在内的牙齿畸形综合征有关。microdontia,牛磺酸症,牙本质形成受损。
Objective: To investigate dental anomalies and the molecular etiology of a patient with Ellis−van Creveld syndrome and two patients with Bardet−Biedl syndrome, two examples of ciliopathies. Patients and Methods: Clinical examination, radiographic evaluation, whole exome sequencing, and Sanger direct sequencing were performed. Results: Patient 1 had Ellis−van Creveld syndrome with delayed dental development or tooth agenesis, and multiple frenula, the feature found only in patients with mutations in ciliary genes. A novel homozygous mutation in EVC2 (c.703G>C; p.Ala235Pro) was identified. Patient 2 had Bardet−Biedl syndrome with a homozygous frameshift mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7. Patient 3 had Bardet−Biedl syndrome and carried a heterozygous mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7 and a homozygous mutation in BBS2 (c.209G>A; p.Ser70Asn). Her clinical findings included global developmental delay, disproportionate short stature, myopia, retinitis pigmentosa, obesity, pyometra with vaginal atresia, bilateral hydronephrosis with ureteropelvic junction obstruction, bilateral genu valgus, post-axial polydactyly feet, and small and thin fingernails and toenails, tooth agenesis, microdontia, taurodontism, and impaired dentin formation. Conclusions: EVC2, BBS2, and BBS7 mutations found in our patients were implicated in malformation syndromes with dental anomalies including tooth agenesis, microdontia, taurodontism, and impaired dentin formation.