Ehlers-Danlos综合征是一类复杂的遗传性结缔组织疾病,是由多个基因突变引起的粘多糖合成障碍,影响细胞外基质的功能,以关节活动度过大、皮肤松弛和组织脆性为显著特征。其中B4GALT7基因突变引起的Ehlers-Danlos患者还可表现出身材矮小、前臂骨骼和关节的异常、弯曲的四肢等,这一型患者目前报道的仅有8例。本文报道一例国内确诊的B4GALT7基因突变患者,运用二代测序技术发现两个新的氨基酸突变p.(Arg141Gln)和p.(Arg234His)。同时进行文献回顾,与之前报道病例的临床表型和基因型进行比较,明确该型Ehlers-Danlos综合征常见的共同特征、诊断标准、致病基因,进一步比较不同突变位点引起的临床表现,尝试对B4GALT7基因不同位点突变对蛋白质功能的影响进行解释,帮助临床医生提高对这一罕见疾病的认识,提高诊断率,改善患者的预后。 Ehlers-Danlos syndrome is a complex hereditary connective tissue disease. It is caused by multiple gene mutations which result in the dysfunction of Mucopolysaccharide synthesis and affect the function of extracellular matrix. It is characterized by joint hypermobility, skin hyperextension and tissue fragility. Among all subtypes of Ehlers-Danlos syndrome, one type caused by B4GALT7 gene mutation can also manifest short stature, abnormalities of forearm bone and joint, curved limbs and so on. So far, there are only 8 cases reported worldwide on this type of Ehlers-Danlos syndrome. In this paper, we reported a new case of B4GALT7 gene mutation patient diagnosed in China and two new amino acid mutations p.(Arg141Gln) and p.(Arg234His) were found by high-throughput sequencing technology. Further, we do a literature review, compared all the clinical phenotype and genotype of previously reported cases and this case, clarify the common manifestations, diagnostic criteria and pathogenic genes of this type of Eh-lers-Danlos syndrome. Also, we compared the different clinical manifestations caused by different sites’ mutations of the B4GALT7 gene, tried to explain the effects of different sites’ mutations on protein function. All above can help clinicians to improve their understanding on this rare disease, increase the diagnosis rate, and improve the prognosis of this kind of patients as much as possible.
患儿,女,第一胎第一产,孕周37+剖宫产出生,出身体重2.25 kg,出生身长42 cm。1岁20天时因“生长缓慢”至我院生长发育门诊就诊,体格检查:身高68.2 cm (相当于同年龄、同性别儿童身高的−2.88SD),体重7.0 kg (相当于同年龄、同性别儿童身高的−2.97SD),头围42.5 cm,双足轻度外翻,其余部位未见明显异常。患儿父亲身高171 cm,母亲155 cm,排除家族性身材矮小。给与营养干预治疗,观察生长速度,定期随访。患儿3岁时复诊,身高82.7 cm (−3.68SD),实验室检查:甲状腺功能、生长激素、类胰岛素样生长因子、生化全项均正常,排除明显的影响生长发育的疾病。
患儿4岁1个月时再次复诊,体格检查:身高88.2 cm (−4.03SD),体重11.2 kg (−3.88SD),三角脸、扁平脸、眼球突出,前额宽,鼻梁塌陷、小下颌,右前臂轻度弯曲、活动受限,双足外翻,肌张力轻度低下,皮肤柔软苍白(因涉及患者隐私未提供照片)。追问病史得知,患儿患有“先天性青光眼”,与生后16天行青光眼手术治疗,现恢复良好。右臂“先天性尺桡骨融合”未行矫正手术。患儿家长拒绝进行全身骨骼的X光检查。因患儿存在多部位的异常及明显的身材矮小,考虑存在基因异常综合征的可能,建议患者进行矮小症相关基因检测。二代测序结果检出患儿存在B4GALT7基因两个位点的突变,对其父母进行一代测序验证,患儿的两个突变位点分别来自父亲和母亲,详细信息见表1和图1。基因检测结果显示该患儿符合EDS伴矮小和肢体异常的诊断,据2017年对EDS的最新国际分型,应诊断为spEDS-B4GALT7。
武华红,李辉. B4GALT7基因变异型Ehlers-Danlos综合征一例及文献复习 Ehlers-Danlos Syndrome with B4GALT7 Mutation: A Case Report and Literature Review[J]. 亚洲儿科病例研究, 2018, 06(03): 19-26. https://doi.org/10.12677/ACRP.2018.63004
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