Congenital Fibrinogen Deficiency Caused by Novel FGG Gene Mutation / 中国实验血液学杂志

OBJECTIVE@#To detect and analyze coagulation related indexes and genotypes of a patient with congenital fibrinogen deficiency and his family members, and to investigate the possible molecular pathogenesis.@*METHODS@#Four peripheral blood samples (proband and 3 family members) were collected and the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg), D-Dimer and eight coagulation factor indicators were detected. All exons and flanking sequences of the FGA, FGB, and FGG genes encoding the three peptide chains of fibrinogen were sequenced and analyzed by bioinformatics.@*RESULTS@#Among the eight coagulation factors of the proband and the elder sister, F Ⅴ and F Ⅷ were slightly higher, TT was significantly prolonged, and Fg was significantly reduced. Sequencing results showed that c.901C>T heterozygous mutation existed in the FGG gene. Bioinformatics analysis showed that the mutation changed the original protein structure and reduced the number of hydrogen bonds.@*CONCLUSION@#The fibrinogen gamma chain c.901C>T heterozygous mutation is the main cause of congenital fibrinogen deficiency in this family. This mutation is reported for the first time at home and abroad.

Detection of hemophilia A carrier by FⅧ:C/vWFAg ratio / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the cut-off value for coagulation factor Ⅷ activity (FⅧ:C) to von Willebrand factor antigen (vWFAg) ratio which can classify obligatory carriers of hemophilia A and normal females, and assess its feasibility to diagnose suspected carriers in affected families through comparison with the method of gene diagnosis.</p><p><b>METHODS</b>FⅧ:C assay was carried out by a one-stage method in both obligatory carriers and normal females. vWF antigen was measured with ELISA assay. The FⅧ:C/vWF ratio was calculated. Statistic analysis was carried out to determine the cut-off value which can classify the two groups. The ratio was then used to diagnose suspected carriers from families affected with hemophilia A. The results were compared with that by long distance polymerase chain reaction, genetic linkage analysis and/or direct sequencing.</p><p><b>RESULTS</b>The FⅧ:C/vWFAg value for 90.6% of obligatory carriers was under 0.82. Should 0.82 be selected as the cut-off value to diagnose the 42 suspected carriers, most of them can be readily diagnosed. The results were all in agreement with that of genetic analysis.</p><p><b>CONCLUSION</b>Cut-off value of FⅧ:C/vWFAg may be used for initial diagnose of the suspected carriers from families affected with hemophilia A. The method is quite convenient and reliable.</p>

Identification of a novel allele HLA-DRB1*1219 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify a novel HLA DRB1 allele in a Chinese leukemia family.</p><p><b>METHODS</b>A new HLA-DRB1 allele was initially detected by polymerase chain reaction-sequence specific primer and unusual reaction pattern by Luminex RSSO, then DNA sequencing was performed to identify the sequence of the novel allele.</p><p><b>RESULTS</b>The DNA sequencing revealed the presence of the new allele which differs from the closest matching HLA-DRB1*120201 by a single nucleotide substitution at position (341 C > T in exon 2), resulting in an amino acid change from Ala to Val at coden 85.</p><p><b>CONCLUSION</b>A novel allele was confirmed by DNA sequencing and has been designated HLA-DRB1*1219 by the WHO Nomenclature Committee.</p>