TMEM38B纯合突变导致罕见ⅪⅤ型成骨不全症

A homozygous mutation in TMEM38B causes rare osteogenesis imperfecta type ⅪⅤ

目的调查一例成骨不全症(OI)患者的临床特点,并研究患者及其家系的致病基因突变。方法纳入一例幼年起病、反复轻微外力下发生多次骨折的维吾尔族儿童,详细询问病史,评估其骨转换生化指标、骨密度和骨骼X线特点。采用二代靶向捕获测序技术检测致病基因突变,并用Sanger测序法进行验证。结果先证者血清β-胶原降解产物升高,影像学提示胸腰椎骨质疏松和四肢长骨纤细且骨皮质菲薄。基因检测提示患者存在TMEM38B第4外显子c.507G>A纯合突变,导致蛋白质截短突变(p.W169X),患者父母均为上述基因突变的携带者。结论首次在罹患罕见ⅪⅤ型成骨不全症的维吾尔族儿童中检出TMEM38B突变,拓展了对TMEM38B突变导致罕见类型成骨不全症的认识。

Objective To investigate the phenotype of a boy with osteogenesis imperfecta（ OI） and detect the pathogenic gene mutation in his family. Methods The clinical data of a uygur ethnic boy was investigated in detail,who suffered from early onset repeated fragile fractures. Bone turnover biomarkers,bone mineral density（ BMD）and bone morphology were evaluated. The pathogenic mutations in this patient were investigated by targeted nextgeneration sequencing and subsequently confirmed by Sanger sequencing. Results Serum β-cross linked C-telopeptide of type Ⅰ collagen was elevated. Radiological assessment revealed a generalized osteoporosis in thoracolumbar spine,slender long bone with thin cortices. The pathogenic mutations in TMEM38 B were detected as follow：a homozygous mutation c.507 G〉A transition in exon 4,which would generate a new downstream termination codon（ p. W169 X）. His parents were heterozygous carriers of the mutation.Conclusions Mutation in TMEM38 B is identified for the first time in a uygur ethnic boy with extremely rare autosomal recessive OI type ⅪⅤ. The clinical and genetic findings expands our understanding of rare OI induced by TMEM38 B mutation.