1临床资料患儿,马某,女,8岁。2岁时发现视力差,在外院诊断为"双眼青光眼",给予布林佐胺滴眼液、布林佐胺噻吗洛尔滴眼液、拉坦前列素滴眼液等眼药水降眼压治疗。眼压控制不佳,双眼眼压在30~45 mmHg(1 mmHg=0.133 k Pa)波动,于...1临床资料患儿,马某,女,8岁。2岁时发现视力差,在外院诊断为"双眼青光眼",给予布林佐胺滴眼液、布林佐胺噻吗洛尔滴眼液、拉坦前列素滴眼液等眼药水降眼压治疗。眼压控制不佳,双眼眼压在30~45 mmHg(1 mmHg=0.133 k Pa)波动,于2019年7月24日来中国中医科学院眼科医院就诊。展开更多
Objective： Axenfeld-Rieger syndrome （ARS） is phenotypically and genetically heterogeneous. In this study we identified the underlying genetic defect in a Chinese family with ARS. Methods： A detailed family history...Objective： Axenfeld-Rieger syndrome （ARS） is phenotypically and genetically heterogeneous. In this study we identified the underlying genetic defect in a Chinese family with ARS. Methods： A detailed family history and clinical data were recorded. The ocular phenotype was documented using slit-lamp photography and systemic anomalies were also documented where available. The genomic DNA was extracted from peripheral blood leukocytes. All coding exons and intron-exon junctions of paired-like homeodomain transcription factor 2 （PITX2） gene and the forkhead box C1 （FOXC1） gene were amplified by polymerase chain reaction （PCR） and screened for mutation by direct DNA sequencing. Variations detected in exon 5 of PITX2 were further evaluated with cloning sequencing. The exon 5 of PITX2 was also sequenced in 100 healthy controls, unrelated to the family, for comparison. Structural models of the wild type and mutant homeodomain of PITX2 were investigated by SWISS-MODEL. Results： Affected individuals exhibited variable ocular phenotypes, whereas the systemic anomalies were similar. After direct sequencing and cloning sequencing, a heterozygous deletion/insertion mutation c. 198_201delinsTTTCT （p.M661fs＊133） was revealed in exon 5 of PITX2. This mutation co-segregated with all affected individuals in the family and was not found either in unaffected family members or in 100 unrelated controls. Conclusions： We detected a novel frameshift mutation p.M661fs＊133 in PITX2 in a Chinese family with ARS. Although PITX2 mutations and polymorphisms have been re- ported from various ethnic groups, we report for the first time the identification of a novel deletion/insertion mutation that causes frameshift mutation in the homeodomain of PITX2 protein.展开更多
AIM： To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome （ARS） and characterize the molecular defect in PITX2 in the family. METHODS： Patients presented with typical ARS from a Chin...AIM： To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome （ARS） and characterize the molecular defect in PITX2 in the family. METHODS： Patients presented with typical ARS from a Chinese family were investigated. We performed genome- wide linkage scan and exome sequencing to identify the pathogenic mutations, Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing, Real-time polymerase chain reaction （RT- PCR） and Western blotting were performed to verify the expression of the pathogenic gene. RESULTS： Genome-wide linkage and exome sequencing analyses showed PITX2 as the disease candidate gene. A〉G substitution at position -11 of 3＇ss of exon 5 （IVS5- 11A〉G） that co-segregated with the disease phenotype was discovered in the family. The PITX2 messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family, CONCLUSION： Our findings implicate the first intronic mutation of the PITX2 gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of PITX2 have been found.展开更多
BACKGROUND Axenfeld-Rieger syndrome(ARS)is an autosomal dominant genetic disease characterized by ocular developmental disorders and its association with torsion of wandering spleen(WS)has not been reported to date to...BACKGROUND Axenfeld-Rieger syndrome(ARS)is an autosomal dominant genetic disease characterized by ocular developmental disorders and its association with torsion of wandering spleen(WS)has not been reported to date to the best of our knowledge.This study aimed to describe a rare case of ARS observed at our emergency department.CASE SUMMARY A 25-year-old female presented with a constant lower abdominal pain of increasing severity.Diagnostic computed tomography with intravenous contrast material showed a non-homogenously enhanced splenic parenchyma with a twisted vascular pedicle.Further,an emergent laparoscopic exploration was performed,and an ischemic spleen without its normal ligamentous attachments was noted.Notably,the spleen did not regain its normal vascularity after detorsion;thus,we performed the laparoscopic total splenectomy.The postoperative course was uneventful,and the patient was discharged on the 5th postoperative day.This case demonstrates a rare association of WS and ARS.CONCLUSION Early diagnosis of WS in the emergency department is important to prevent pedicle torsion or splenic necrosis and to avoid splenectomy.展开更多
文摘1临床资料患儿,马某,女,8岁。2岁时发现视力差,在外院诊断为"双眼青光眼",给予布林佐胺滴眼液、布林佐胺噻吗洛尔滴眼液、拉坦前列素滴眼液等眼药水降眼压治疗。眼压控制不佳,双眼眼压在30~45 mmHg(1 mmHg=0.133 k Pa)波动,于2019年7月24日来中国中医科学院眼科医院就诊。
基金Project supported by the Qianjiang Talents Project of Zhejiang Province(No.2010R10067)the Zhejiang Key Innovation Team Project of China(No.2009R50039)the Zhejiang Key Laboratory Foundation of China(No.2011E10006)
文摘Objective： Axenfeld-Rieger syndrome （ARS） is phenotypically and genetically heterogeneous. In this study we identified the underlying genetic defect in a Chinese family with ARS. Methods： A detailed family history and clinical data were recorded. The ocular phenotype was documented using slit-lamp photography and systemic anomalies were also documented where available. The genomic DNA was extracted from peripheral blood leukocytes. All coding exons and intron-exon junctions of paired-like homeodomain transcription factor 2 （PITX2） gene and the forkhead box C1 （FOXC1） gene were amplified by polymerase chain reaction （PCR） and screened for mutation by direct DNA sequencing. Variations detected in exon 5 of PITX2 were further evaluated with cloning sequencing. The exon 5 of PITX2 was also sequenced in 100 healthy controls, unrelated to the family, for comparison. Structural models of the wild type and mutant homeodomain of PITX2 were investigated by SWISS-MODEL. Results： Affected individuals exhibited variable ocular phenotypes, whereas the systemic anomalies were similar. After direct sequencing and cloning sequencing, a heterozygous deletion/insertion mutation c. 198_201delinsTTTCT （p.M661fs＊133） was revealed in exon 5 of PITX2. This mutation co-segregated with all affected individuals in the family and was not found either in unaffected family members or in 100 unrelated controls. Conclusions： We detected a novel frameshift mutation p.M661fs＊133 in PITX2 in a Chinese family with ARS. Although PITX2 mutations and polymorphisms have been re- ported from various ethnic groups, we report for the first time the identification of a novel deletion/insertion mutation that causes frameshift mutation in the homeodomain of PITX2 protein.
基金Supported by China Postdoctoral Science Foundation Funded Project(No.2017M612211)the National Natural Science Foundation of China(No.81300742+2 种基金No.81600721)the Shandong Province Medical and Health Technology Development Project(No.2016WS0265)the Science and Technology Plan of Qingdao(No.15-9-1-35-jch)
文摘AIM： To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome （ARS） and characterize the molecular defect in PITX2 in the family. METHODS： Patients presented with typical ARS from a Chinese family were investigated. We performed genome- wide linkage scan and exome sequencing to identify the pathogenic mutations, Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing, Real-time polymerase chain reaction （RT- PCR） and Western blotting were performed to verify the expression of the pathogenic gene. RESULTS： Genome-wide linkage and exome sequencing analyses showed PITX2 as the disease candidate gene. A〉G substitution at position -11 of 3＇ss of exon 5 （IVS5- 11A〉G） that co-segregated with the disease phenotype was discovered in the family. The PITX2 messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family, CONCLUSION： Our findings implicate the first intronic mutation of the PITX2 gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of PITX2 have been found.
文摘BACKGROUND Axenfeld-Rieger syndrome(ARS)is an autosomal dominant genetic disease characterized by ocular developmental disorders and its association with torsion of wandering spleen(WS)has not been reported to date to the best of our knowledge.This study aimed to describe a rare case of ARS observed at our emergency department.CASE SUMMARY A 25-year-old female presented with a constant lower abdominal pain of increasing severity.Diagnostic computed tomography with intravenous contrast material showed a non-homogenously enhanced splenic parenchyma with a twisted vascular pedicle.Further,an emergent laparoscopic exploration was performed,and an ischemic spleen without its normal ligamentous attachments was noted.Notably,the spleen did not regain its normal vascularity after detorsion;thus,we performed the laparoscopic total splenectomy.The postoperative course was uneventful,and the patient was discharged on the 5th postoperative day.This case demonstrates a rare association of WS and ARS.CONCLUSION Early diagnosis of WS in the emergency department is important to prevent pedicle torsion or splenic necrosis and to avoid splenectomy.
