Preliminary functional analysis of a novel mutation in GATA-4 gene in Chinese patients with congenital cardiac septal defects / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To perform the functional analysis of a novel H436Y mutation of GATA-4 gene identified in Han Chinese patients with congenital cardiac septal defects.</p><p><b>METHODS</b>Using bioinformatics to predict if the H436Y mutation in the GATA-4 gene affects its protein function. H436Y mutation in the GATA-4 gene was generated by Quick Change Lightning site-directed mutagenesis kit and verified by DNA sequencing. GATA-4-wt or GATA-4-mut DNA was cotransfected into Hela cells with DNA for the luciferase reporter gene atrial natriuretic factor (ANF), and luciferase activity was measured by an LKB luminometer 48 h after transient transfection.</p><p><b>RESULTS</b>Alignment of the GATA-4 amino acid sequence indicated that the histidine residue at position 436 was conserved, and H436Y mutation in the GATA-4 gene is expected to affect its protein function. The H436Y mutation significantly reduced the transcriptional activation of downstream reporter ANF when compared to wild-type GATA-4 (P<0.01).</p><p><b>CONCLUSION</b>The mutation c.1306C-->T of the GATA-4 gene impaired the activation of the downstream target, suggesting that the H436Y mutation in the C-terminal region of the GATA-4 gene might prevent its biological function.</p>

Clinical and molecular genetic analysis for 7 patients from 5 pedigrees with 17a-hydroxylase/17, 20 lyase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and genetic characteristics of 7 patients from 5 families with 17a-hydroxylase/17,20 lyase deficiency (17OHD) and the CYP17A1 mutation in Chinese.</p><p><b>METHODS</b>Clinical features and laboratory data were collected from 5 families with 17OHD. PCR direct sequencing was performed to screen the mutation of CYP17A1 gene of the patients. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing were performed to screen the mutations of CYP17A1 gene in 288 healthy individuals from Shandong province.</p><p><b>RESULTS</b>Seven patients (5 of them were 46,XX; 2 were 46,XY) had typical clinical presentation of sexual infantilism, hypertension and hypokalemia. Hormone profile indicated decreased plasma cortisol and sex hormones, and elevated blood adrenocorticotrophic hormone (ACTH). TAC329AA and H373L in exon 6 and D487_F489del in exon 8 were identified from the patients. One heterozygote for D487_F489del was identified in 288 healthy controls.</p><p><b>CONCLUSION</b>The TAC329AA and D487_F489del of the CYP17A1 gene were the most frequent mutations in Chinese with 17OHD.There might be certain frequency of heterozygotes for D487_F489del in Chinese population.</p>

Association between GATA-4 mutations and congenital cardiac septal defects in Han Chinese patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To elucidate the association between GATA-4 gene mutations and congenital cardiac septal defects in Han Chinese patients.</p><p><b>METHODS</b>Fifty Han Chinese patients with congenital cardiac septal defects and 100 normal subjects with the same ethnical background were studied. Total six exons and the intron-exon boundaries of GATA-4 were amplified by the polymerase chain reaction. The polymerase chain reaction products were purified and directly sequenced with automatic sequencer.</p><p><b>RESULTS</b>Two novel heterozygous mutations were discovered in the GATA-4 gene of patients with congenital cardiac septal defects, His28Tyr in exon 2 and His436Tyr in exon 7 respectively, which were absent in the control population and not reported in the SNP database (http://www.ncbi.nlm.nih.gov/SNP).</p><p><b>CONCLUSION</b>Our finding suggests that the mutations in the transcription factor GATA-4 may be related to congenital cardiac septal defects in Han Chinese patients.</p>