A novel mutation in a patient with congenital coagulation factor XII deficiency

Human coagulation factor Ⅻ （FⅫ）, also called Hageman factor, is a plasma plycoprotein that is functionally deficient in individuals with Hageman trait; which is an inherited trait discovered by chance during preoperative blood coagulation screening tests. FⅫ is a single-chain 596-amino-acid zymogen of a serine protease with an approximate molecular weight of 80 000 FⅫ appears to play an important role in blood coagulation,     

A novel mutation in a patient with congenital coagulation factor Ⅻ deficiency

Human coagulation factor Ⅻ(FⅫ),also called Hageman factor,is a plasma plycoprotein that is functionally deficient in individuals with Hageman trait:which is an inhefited trait discovered by chance during preoperative blood coagulation screening tests.FⅫ is a single-chain 596-amino-acid zymogen of a serine protease with an approximate molecular weight of 80 000.     

A novel gene mutation of K317N in a Chinese Brugada syndrome family

SCN５Ageneencodinghumancardiacvoltage－gatedsodium－channelaunitisresponsibleforBrugadasyndrome，adiseasecharacterizedbySTsegmentelevationinECGprecordialleadofV１－V３withorwithoutrightbundle－branchblock，andincasesinwhichsuddendeathorsyncopeoccurs，polymorphicventriculartachycardia（VT）orventricularfibrillation（VF）maybepresent．Uptodate，morethan１０differentmutations，alllocatedinSCN５Agene，havebeenidentified．TounderstandtheassociationofSCN５Agenemutationwiththispotentiallyfat…     

A novel mutation, Y255X, of the ARSB gene in a Chinese family with mucopolysaccharidosis type Ⅵ

Mucopolysaccharidoses (MPS) are lysosomal storage diseases with defectivedegradation of glycosaminoglycans. Mucopolysaccharidosis type Ⅳ( MPS Ⅳ )or Maroteaux-Lamy syndrome is caused by defective arylsulfatase B in the lysosomes ( ARSB; Nacetylgalactosamine-4-sulfatase, EC 3.1.6. 12 ) . The clinical manifestations of MPS VI include coarse facial features, growth retardation, short stature, skeletal malformations, hepatosplenomegaly, corneal clouding,and cervical myelopathy. Heart failure is the usual cause of death in the second or third decade of life. Despite all the physical disabilities, the intellect of MPS Ⅳ patients is preserved.     

A novel KIAA0196（SPG8） mutation in a Chinese family with spastic paraplegia

Hereditary spastic paraplegia （HSP） is one of the most.heterogeneous genetic neurodegenerative diseases,caused by mutations in more than 50 different genes.The eighth HSP locus,SPG8,is on chromosome 8p24.13.SPG8 is a rare autosomal dominant-HSP （AD-HSP） caused by mutations in the KIAA0196 gene,with only seven SPG8families described to date.1 Here,we described the clinical characteristics of AD-HSP caused by a novel mutation in the KIAA0196 gene in a Chinese family.     

Multiple endocrine neoplasia type 2B caused by a single point mutation in RET proto-oncogene in a Chinese patient

Multiple endocrine neoplasia type 2(MEN 2) is a hereditary syndrome which can present itself either in a familial form.characterized by a dominant pattern of inheritance,or in a sporadic form.It can be subdivided into multiple endoerine neoplasia type 2A(MEN-2A),multiple endoerine neoplasia type 2B(MEN-2B).and familial medullary thyroid careinoma(FMTC).     

Ethnic-specific splicing mutation of the carnitine-acylcarnitine translocase gene in a Chinese neonate presenting with sudden unexpected death

Carnitine acylcarnitinetranslocase (CACT )deficiency(OMIM 2 12 138)isanautosomalrecessivediseasecausedbymutationsoftheSLC2 5A2 0gene [solutecarrierfamily 2 5(carnitine/acylcarnitinetranslocase) ,member 2 0 ] Thegenehasanopenreadingframeof 90 3bp ,1mappedtochromosome 3p2 1 31byinsituhybridization ,2 　andencodesaproteinhavingthreerepeatedhomologousdomains,eachabout 10 0aminoacidsinlength—acharacteristicfeatureofmitochondrialtransportproteins 3,4　CACTisessentialinlong chainfattyacidoxida…     

Detection by denaturing gradient gel electrophoresis of an Arg1689Cys mutation in a Chinese patient with mild hemophilia A.

OBJECTIVE To detect gene defects of factor VIII (F VIII) in Chinese hemophilia A patients.

METHODS 3' end of exon 14 of F VIII gene from a mild hemophilia A patient of Chinese origin was amplified by polymerase chain reaction (PCR) and identified mutations by denaturing gradient gel electrophoresis (DGGE) combining with direct sequencing.

RESULTS An upward shift band was detected by DGGE in W381. Direct sequencing demonstrated a C to T transition resulting in substitution of Arg1689Cys within a thrombin activation site of mature F VIII protein, which created a unique a thrombin activation site of mature F VIII protein, which created a unique PstI site in amplified fragment of F VIII.

CONCLUSIONS The association of PCR and DGGE can detect a single base substitution; the Arg1689Cys mutation that inhibited activation of F VIII by thrombin is a molecular defect associated with hemophilia A in W381.

     

Three novel FOXL2 gene mutations in Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome

Blepharophimosis-ptosis-epicanthus inversus Psyndrome （BPES, OMIM # 110100） is a rare autosomal dominant disorder affecting the eyelid and ovarian development. When co-occurred together, it is type Ⅰ and when only the eyelid abnormalities are present, it is type Ⅱ. Both types had been mapped to the same locus 3q23 on the basis of cytogenetic rearrangements 1-3 and linkage analyses. 4-6 Subsequently,     

A novel mitochondrial tRNA gene mutation in a chinese family with dilated cardiomyopathy and sensorineural deafness

Objective： To determine whether a mutation of mitochondrial DNA induces familial dilated cardiomyopathy in Chinese families with cardiomyopathy, and analyzed the correlation between the genotype and phenotype. Methods： Affected members in three Chinese families of the familial dilated cardiomyopathy underwent clinical evaluation and DNA analysis. Polymerase chain reaction and direct DNA sequencing were used to screen for mitochondrial DNA mutation. The type of mtDNA variations and clinical situation were analysed on the patients with mitochondrial DNA mutation. Results： The mitochondrial A3434G mutation was identified in one of the three families,the 3434 th nucleotide A was replaced by G, which led to change of amino acid. No mutations were identified in the clinically unaffected members of the family and all members of the other two families. Conclusion： This study indicates that the mitochondrial A3434G mutation maybe related with familial dilated cardiomyopathy and deafness.     

A mutation in the type Ⅱ hair keratin KRT86 gene in a Han family with monilethrix

Monilethrix, a congenital disease of hair, is usually associated with mutations in keratin genes, like KRT81, KRT83 and KRT86. We conducted this study to investigate the mutation of type Ⅱ human basic hair keratin hHb/ KRT gene in a Han family with monilethrix and obtain information for potential pathogenic mechanism study of monilethrix. Peripheral blood samples were drawn for genomic DNA detection. Exon 1 and exon 7 of the KRT81, KRT83 and KRT86 genes were amplified by PCR. All PCR products were sequenced...     

Exercise test on the patients with normokalaemic periodic paralysis from a Chinese family with a mutation in the SCN4A gene

Background Normokalaemic periodic paralysis （normoKPP） is characterized by transient and recurrent myoasthenia, and some patients also show muscle stiffness induced by cold exposure （paramyotonia congenita, PMC）. It is caused by a mutation in the muscle voltage gated sodium channel alpha subunit （SCN4A） gene. Due to the diversity of the clinical manifestations of patients, it is difficult for clinicians to differentiate some of patients with atypical normoKPP from those who suffer from other periodic paralysis and nondystrophic myotonia. So far, for normoKPP there are almost no ways to assist definite diagnosis besides genetic screening. This research was designed to evaluate an exercise test （ET） in confirming the diagnosis of normoKPP and in assessing the therapeutic effectiveness of some drugs on this disease. Methods ET, described by McMains, was performed on six subjects from a Chinese family, including four patients with overlapping disease of normoKPP and PMC caused by a mutation of SCN4A Met1592Val that is identified by genetic analysis and two normal control members. The change of compound muscle action potential （CMAP） was recorded. Besides the family, two patients were also tested during treatments with acetazolamide. Results All patients showed a slight increase in CMAP immediately after exercise, followed by an abnormal gradual decline, which reached its nadir 25-30 minutes after exercise. CMAP amplitude dropped by more than 40% in patients but less than 23% in controls. In the patients who received treatment with acetazolamide, the change of CMAP amplitude was less than 28% and, at any fixed times, less than pretreatment values. Conclusions The ET may be used as a predictive, easy and reliable method of diagnosing normoKPP under conditions without genetic screening help, and is an objective way to evaluate the therapeutic effectiveness. According to different response patterns, the ET may also be helpful in reducing the scope of genetic screening.     

Identification of a novel lethal fibrillin-1 gene mutation in a Chinese Marfan family and correlation of 3’ fibrillin-1 gene mutations with phenotype

Background Mutations in the fibrillin-1 gene have been identified in patients with Marfan syndrome （MFS）. This study aimed to identify the molecular defects in the fibrillin-1 gene in a Chinese family with Marfan syndrome, accompanied by aortic aneu rysms/dissection. Methods Two patients and one non-carrier in the family underwent complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of these individuals in the family as well as 50 healthy normal controls. Polymerase chain reaction amplification and direct sequencing of all 65 coding exons of fibrillin-1 gene were analyzed. Results We found a novel mutation （c.8547T〉G, p.Tyr2849X） in exon 65 of fibrillin-1 gene in a Chinese proband with Marfan syndrome, accompanied by aortic aneurysms/dissection. Sudden death at a young age of affected members was seen due to aortic aneurysms/dissection. By evaluating genotype-phenotype correlations of patients with mutations in the 3＇ end of fibrillin-1 gene （exons 64 and 65）, we also found that the presence of nonsense mutations occurring in exons 64 and 65 appeared to be an indicator of early-onset aortic risk and sudden death. Conclusions These results expand the mutation spectrum of fibrillin-1 gene and help in the study of the molecular pathogenesis of Marfan syndrome, indicating that mutations occurring in the 3＇ end of fibrillin-1 gene may play an independent functional role in the pathogenesis of Marfan syndrome.     

Brugada syndrome masquerading as acute myocardial infarction in a patient presenting with ventricular fibrillation

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Identification of a novel missense mutation in Wilson''s disease gene.

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A novel splicing variant in the TMC1 gene causes non-syndromic hearing loss in a Chinese family

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