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

摘要: 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。

Abstract: 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.