BACKGROUND Oral-facial-digital syndrome type 1(OFD1) is a rare ciliopathy mainly with an Xlinked dominant pattern of inheritance, which is caused by mutations in the OFD1 gene. The OFD1 protein is located within the c...BACKGROUND Oral-facial-digital syndrome type 1(OFD1) is a rare ciliopathy mainly with an Xlinked dominant pattern of inheritance, which is caused by mutations in the OFD1 gene. The OFD1 protein is located within the centrosomes and basal bodies of the primary cilia. It is reported that approximately 15%–50% cases of OFD1 progress to end-stage renal disease(ESRD) following development of polycystic kidney diseases(PKD). Here we report a pair of childhood male twins who presented only renal failure and PKD caused by an OFD1 mutation in China.CASE SUMMARY A pair of 14-year male twins were hospitalized with a complaint of abnormal renal function for nine days. They both complained of ankle pain for 3 mo vs 2 wk, respectively. They denied fever, abdominal pain, daytime or nighttime enuresis, urgency, dysuria, or gross hematuria. Laboratory tests at a local hospital showed renal failure(serum creatinine 485 μmol/L vs 442 μmol/L, blood urea nitrogen 14.7 mol/L vs 14.5 mol/L) and anemia(hemoglobin 88 g/L vs 98 g/L).The twins are monozygotic. There was no abnormal birth, past medical, or family history. Clinical data were analyzed and genetic analysis on PKD was carried out in the twins by next-generation sequencing. The results showed that the twins presented low-molecular-weight proteinuria, hyposthenuria, anemia, renal failure, and renal polycystic changes. Genetic tests showed that the twins both carried a hemizygous mutation in exon 19 c.2524 G>A(p. G842 R) of the OFD1 gene. Their mother heterozygously carried the same mutation as the twins but was without any phenotypes while their father was normal.CONCLUSION We have reported a pair of childhood male twins with an OFD1 mutation who presented ESRD and PKD but without any other phenotypes of OFD1 in China.展开更多
目的对1个口-面-指综合征1型(oral-facial-digital syndrome type 1,OFD1)家系进行致病基因分析,明确其致病变异,为家系的遗传咨询和产前诊断提供依据。方法应用全外显子测序技术对先证者进行基因变异筛查,发现OFD1基因可疑变异位点后,...目的对1个口-面-指综合征1型(oral-facial-digital syndrome type 1,OFD1)家系进行致病基因分析,明确其致病变异,为家系的遗传咨询和产前诊断提供依据。方法应用全外显子测序技术对先证者进行基因变异筛查,发现OFD1基因可疑变异位点后,用Sanger测序技术对该家系成员和100名正常对照进行验证,确定该家系的致病位点。使用X染色体失活分析判断两条X染色体的活性比例,并对家系中孕20周胎儿抽取羊水标本进行产前诊断。结果先证者及家系中所有患者均携带OFD1基因c.1189_1192delAATC(p.Q398Lfs*2)杂合变异,而家系中正常成员和100名正常对照均未检测到此变异。孕妇及其妹妹存在X染色体非随机失活,家系中其余女性患者均为X染色体随机失活。产前诊断结果为胎儿携带OFD1基因c.1189_1192delAATC(p.Q398Lfs*2)杂合变异。结论OFD1基因c.1189_1192delAATC(p.Q398Lfs*2)杂合变异是该家系的致病原因,新变异的检出丰富了OFD1基因变异谱,但家系内表型差异性的原因仍需要更深入的研究证实。展开更多
文摘BACKGROUND Oral-facial-digital syndrome type 1(OFD1) is a rare ciliopathy mainly with an Xlinked dominant pattern of inheritance, which is caused by mutations in the OFD1 gene. The OFD1 protein is located within the centrosomes and basal bodies of the primary cilia. It is reported that approximately 15%–50% cases of OFD1 progress to end-stage renal disease(ESRD) following development of polycystic kidney diseases(PKD). Here we report a pair of childhood male twins who presented only renal failure and PKD caused by an OFD1 mutation in China.CASE SUMMARY A pair of 14-year male twins were hospitalized with a complaint of abnormal renal function for nine days. They both complained of ankle pain for 3 mo vs 2 wk, respectively. They denied fever, abdominal pain, daytime or nighttime enuresis, urgency, dysuria, or gross hematuria. Laboratory tests at a local hospital showed renal failure(serum creatinine 485 μmol/L vs 442 μmol/L, blood urea nitrogen 14.7 mol/L vs 14.5 mol/L) and anemia(hemoglobin 88 g/L vs 98 g/L).The twins are monozygotic. There was no abnormal birth, past medical, or family history. Clinical data were analyzed and genetic analysis on PKD was carried out in the twins by next-generation sequencing. The results showed that the twins presented low-molecular-weight proteinuria, hyposthenuria, anemia, renal failure, and renal polycystic changes. Genetic tests showed that the twins both carried a hemizygous mutation in exon 19 c.2524 G>A(p. G842 R) of the OFD1 gene. Their mother heterozygously carried the same mutation as the twins but was without any phenotypes while their father was normal.CONCLUSION We have reported a pair of childhood male twins with an OFD1 mutation who presented ESRD and PKD but without any other phenotypes of OFD1 in China.
文摘目的对1个口-面-指综合征1型(oral-facial-digital syndrome type 1,OFD1)家系进行致病基因分析,明确其致病变异,为家系的遗传咨询和产前诊断提供依据。方法应用全外显子测序技术对先证者进行基因变异筛查,发现OFD1基因可疑变异位点后,用Sanger测序技术对该家系成员和100名正常对照进行验证,确定该家系的致病位点。使用X染色体失活分析判断两条X染色体的活性比例,并对家系中孕20周胎儿抽取羊水标本进行产前诊断。结果先证者及家系中所有患者均携带OFD1基因c.1189_1192delAATC(p.Q398Lfs*2)杂合变异,而家系中正常成员和100名正常对照均未检测到此变异。孕妇及其妹妹存在X染色体非随机失活,家系中其余女性患者均为X染色体随机失活。产前诊断结果为胎儿携带OFD1基因c.1189_1192delAATC(p.Q398Lfs*2)杂合变异。结论OFD1基因c.1189_1192delAATC(p.Q398Lfs*2)杂合变异是该家系的致病原因,新变异的检出丰富了OFD1基因变异谱,但家系内表型差异性的原因仍需要更深入的研究证实。
