Achondroplasia （ACH） is the most common form of skeletal dysplasia characterized by disproportionately short stature, lumbar lordosis, relative macrocephaly and other skeletal anomalies resulting from a defect in th...Achondroplasia （ACH） is the most common form of skeletal dysplasia characterized by disproportionately short stature, lumbar lordosis, relative macrocephaly and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. The combined frequency of the disease has been estimated to be 1 in 15 000 live births.1 ACH is inherited in autosomal dominant fashion with a complete penetrance, more than 80% of affected individuals have de novo mutations associated with increased paternal age.展开更多
Background：Von Hippel-Lindau （VHL） disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene.Few studies have documented the clinical phenotype and genetic basis of the occurrence of V...Background：Von Hippel-Lindau （VHL） disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene.Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China.This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China,and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.Methods：An epidemiological investigation of family members was done to collect the general information.A retrospective study of clinical VHL cases was launched to collect the relative clinical data.Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family.The VHL gene screening was performed by directly analyzing DNA sequence output.At last,we summarized the VHL gene mutation in China by the literature review.Results：A five-generation North-western Chinese family afflicted with VHL disease was traced in this research.The family consisted of 38 living family members,of whom nine were affected.The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas （8）,central nervous system hemangioblastomas （3）,pancreatic endocrine tumors （2）,pancreatic cysts （3）,renal cysts （4）,and paragangliomas （2）.A linkage analysis resulted in a high maximal LOD score of 8.26 （theta =0.0） for the marker D3S1263,which is in the same chromosome region as VHL.Sequence analysis resulted in the identification of a functional C〉T transition mutation （c.499 C〉T,p.R167W） located in exon 3 of the 16th codon of VHL.All affected individuals shared this mutation,whereas the unaffected family members and an additional 100 unrelated healthy individuals did not.To date,49 mutations have been associated with this disease in Chinese populations.The most frequent VHL mutations in China are p.S65 W,p.N78 S,p.R161Q and p.R167 W.Conclusions：The results suppo展开更多
Objective To detect mutations of the retinitis pigmentosa GTPase regulator (RPGR) gene in two Chinese X-linked retinitis pigmentosa families. Methods Fragments of exons 1-19 of the RPGR gene were amplified with intron...Objective To detect mutations of the retinitis pigmentosa GTPase regulator (RPGR) gene in two Chinese X-linked retinitis pigmentosa families. Methods Fragments of exons 1-19 of the RPGR gene were amplified with intronic primers, using genomic DNA as template. The polymerase chain reaction (PCR) products were analysed by single-strand conformation polymorphism (SSCP) and direct sequencing. Mutations were identified by comparing DNA sequences of the patients with those of the normal controls.Results Two novel mutations, c1536delC and E332X, were identified in exons 12 and 9 of the RPGR gene in both families. Each mutation was the first mutation found in their respective exons. Both mutations were predicted to cause premature termination, which resulted in truncated proteins without normal functions of the RPGR products.Conclusions Both mutations are the genetic basis of the pathogenesis in the respective families. Our data might be helpful in analysing the function of the RPGR 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
基金the funds of the National HighTechnology Research and Development Program of China (863 Program, No. 2002BA711A07)the 10th Five Years Key Programs for Science and Technology Development of China (No. 2004BA720A02) the National Natural Science Foundation of China (No. 30470982)
文摘Achondroplasia （ACH） is the most common form of skeletal dysplasia characterized by disproportionately short stature, lumbar lordosis, relative macrocephaly and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. The combined frequency of the disease has been estimated to be 1 in 15 000 live births.1 ACH is inherited in autosomal dominant fashion with a complete penetrance, more than 80% of affected individuals have de novo mutations associated with increased paternal age.
基金This study was supported by funding from the National Science Foundation of China （No. 81072051 and No.81272644）.ACKNOWLEDGMENTS We are indebted to all individuals who participated in or helped with this research project.
文摘Background：Von Hippel-Lindau （VHL） disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene.Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China.This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China,and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.Methods：An epidemiological investigation of family members was done to collect the general information.A retrospective study of clinical VHL cases was launched to collect the relative clinical data.Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family.The VHL gene screening was performed by directly analyzing DNA sequence output.At last,we summarized the VHL gene mutation in China by the literature review.Results：A five-generation North-western Chinese family afflicted with VHL disease was traced in this research.The family consisted of 38 living family members,of whom nine were affected.The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas （8）,central nervous system hemangioblastomas （3）,pancreatic endocrine tumors （2）,pancreatic cysts （3）,renal cysts （4）,and paragangliomas （2）.A linkage analysis resulted in a high maximal LOD score of 8.26 （theta =0.0） for the marker D3S1263,which is in the same chromosome region as VHL.Sequence analysis resulted in the identification of a functional C〉T transition mutation （c.499 C〉T,p.R167W） located in exon 3 of the 16th codon of VHL.All affected individuals shared this mutation,whereas the unaffected family members and an additional 100 unrelated healthy individuals did not.To date,49 mutations have been associated with this disease in Chinese populations.The most frequent VHL mutations in China are p.S65 W,p.N78 S,p.R161Q and p.R167 W.Conclusions：The results suppo
基金supported by the“863”Project(No．86310210) the National Natural Science Foundafion of China(No．3987O4O1)．
文摘Objective To detect mutations of the retinitis pigmentosa GTPase regulator (RPGR) gene in two Chinese X-linked retinitis pigmentosa families. Methods Fragments of exons 1-19 of the RPGR gene were amplified with intronic primers, using genomic DNA as template. The polymerase chain reaction (PCR) products were analysed by single-strand conformation polymorphism (SSCP) and direct sequencing. Mutations were identified by comparing DNA sequences of the patients with those of the normal controls.Results Two novel mutations, c1536delC and E332X, were identified in exons 12 and 9 of the RPGR gene in both families. Each mutation was the first mutation found in their respective exons. Both mutations were predicted to cause premature termination, which resulted in truncated proteins without normal functions of the RPGR products.Conclusions Both mutations are the genetic basis of the pathogenesis in the respective families. Our data might be helpful in analysing the function of the RPGR 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.
