Analysis of deafness gene variant screening of 7875 neonatal cases in Dongying area of Shandong / 中华医学遗传学杂志

OBJECTIVE@#To determine the types and frequency of deafness-related variants among 7875 newborns from Dongying area of Shandong Province.@*METHODS@#One hundred loci of 18 common deafness genes were subjected to semiconductor sequencing. Variant site, frequency and distribution of the variants were analyzed.@*RESULTS@#In total 552 deafness gene variants were detected among the 7875 newborns, which yielded a detection rate of 7.01%. Among these, common variant sites for GJB2, SLC26A4 and GJB3 genes were c.235delC, IVS7-2A>G and c.538C>T, respectively. The variant frequencies of matrilinear inheritance deafness genes MT-CO1, MT-RNR1, MT-TL1 and MT-TS1 were 0.38%, 0.25%, 0.1% and 0.01%, respectively. Four newborns were diagnosed with deafness, among which one had unilateral hearing loss. Analysis of the proportions of neonatal deafness-related variants in five counties of Dongying showed that the highest variant rate for the SLC26A4 gene compared with GJB2 was in Lijin county (51.76% vs. 40%), while the lowest was in Hekou county (30.77% vs. 56.41%).@*CONCLUSION@#The carrier rate of deafness-related variants in Dongying area is higher than other regions of China, which may be attributed to the increased types and variant sites covered by the semiconductor sequencing method compared with the chip method and time-of-flight mass spectrometry. Due to geographical and population aggregation factors, the proportion of deafness variants in the five counties of Dongying differed significantly. Above results may provide a guide for the prevention of congenital deafness in Dongying area.

Mutation analysis of HOXD13 gene in a Chinese family affected with autosomal dominant synpolydactyly / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutation in a Chinese family affected with autosomal-dominant synpolydactyly and to provide the basis for prenatal diagnosis.</p><p><b>METHODS</b>Inheritance pattern was determined by clinical examination and pedigree analysis. Blood samples were obtained from members of the family. Genomic DNA was extracted and sequenced following PCR amplification. Suspected mutation was confirmed by subclone sequencing and agarose gel electrophoresis.</p><p><b>RESULTS</b>A 27 bp expansion mutation in exon 1 of HOXD13 was identified in all affected individuals from the family but not in unaffected members and normal controls. The mutation has caused insertion of 9 alanines in the polyalanine-expansion region of HOXD13 protein.</p><p><b>CONCLUSION</b>A polyalanine-expansion within the HOXD13 probably underlies the disease in this family.</p>

Mutation analysis of EXT2 gene in a family with hereditary multiple exostosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate EXT1 and EXT2 genes mutations in a family with hereditary multiple osteochondromas (HME).</p><p><b>METHODS</b>A four-generation family with HME from Linyi city of Shandong Province was studied. There were 6 affected individuals among the 17 family members. Physical examination and radiographical evaluations were carried out for all family members. Genomic DNA was extracted from peripheral venous blood and the samples were subjected to mutation screening by PCR of the coding regions of EXT1 and EXT2 genes.</p><p><b>RESULTS</b>The family has featured an autosomal dominant inheritance pattern. Sequencing of the EXT1 and EXT2 genes suggested the causative gene in this family was in linkage with the second exon of EXT2. A c.244delG mutation was detected, which has resulted in a frameshift mutation p.Asp81IlefsX30. The mutation was found in all of the 6 affected individuals but not in normal family members. And the mutation has co-segregated with the phenotype.</p><p><b>CONCLUSION</b>The mutation c.244delG in the EXT2 gene is the probably the cause of the disease in this family.</p>

Novel deletion of SPAST in a Chinese family with hereditary spastic paraplegia

<p><b>INTRODUCTION</b>Hereditary spastic paraplegia (HSP) belongs to a large, heterogeneous group of progressive neurodegenerative diseases characterised by progressive lower extremity weakness and spasticity, which is caused by developmental failure or degeneration of motor axons in the corticospinal tract. Classical genetic studies have identified at least 46 genetic loci responsible for HSP.</p><p><b>METHODS</b>A genetic study was conducted on a four-generation Chinese family with autosomal dominant HSP. The SPAST gene was investigated using linkage analysis and direct sequencing. Findings were compared with unaffected family members and 50 normal, unaffected individuals who were matched for geographical ancestry.</p><p><b>RESULTS</b>We identified a novel 14-bp heterozygous deletion that induced a frameshift mutation in exon 15 of SPAST (SPG4). This mutation is predicted to have functional impact and found to cosegregate with the disease phenotype.</p><p><b>CONCLUSION</b>Our results have expanded the mutation spectrum of the SPAST gene. These findings could help clinicians provide prenatal diagnosis of affected foetuses in families with a known history of such neurodegenerative diseases.</p>

Clinical and genetic analysis of a Chinese family affected with X-linked Charcot-Marie-Tooth disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the clinical manifestations and identify causative mutations for a Chinese family affected with X-linked Charcot-Marie-Tooth disease.</p><p><b>METHODS</b>Clinical, electrophysiological and pathological features of the family were carefully analyzed by neurologists. Blood samples were obtained from the proband and other family members. Genomic DNA was extracted. Mutation analysis of GJB1 gene was analyzed with PCR and direct sequencing.</p><p><b>RESULTS</b>The family has fit with X-linked inheritance, and the affected individuals have typical clinical manifestations. A c.614A>G (p.Asn205Ser) mutation was detected in the GJB1 gene in all affected individuals in the family.</p><p><b>CONCLUSION</b>A c.614A>G (p.Asn205Ser) mutation of GJB1 gene is co-segregated with the disease phenotype in this family and probably underlies the disease.</p>

Analysis of gene mutation in a family featuring autosomal dominant May-Hegglin anomaly / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze clinical features and mutation in MYH9 gene for a family featuring autosomal dominant May-Hegglin anomaly.</p><p><b>METHODS</b>Clinical and pathological features of all family members were analyzed. Blood samples were collected from the proband and other family members, and genomic DNA was extracted. Potential mutations of MYH9 gene exons 10, 25, 26, 30, 38 and 40 were screened with PCR and direct sequencing. After a mutation was identified in the proband, other affected members as well as healthy members from this family were analyzed with a pair of primers to amplify the mutant site. The PCR products were digested with Taq I enzyme and analyzed with agarose gel electrophoresis.</p><p><b>RESULTS</b>All affected members had bleeding tendency and typical features including giant platelets, thrombocytopenia and characteristic Dohle body-like leukocyte inclusions. A heterozygous missense mutation c.5521G>A (p.Glu1841Lys) in exon 38 of the MYH9 gene was identified in all affected members from this family.</p><p><b>CONCLUSION</b>The variant, c.5521G>A (p.Glu1841Lys) of MYH9, has co-segregated with the phenotype in the family. The mutant site is a hot spot in Chinese population.</p>

Clinical and neuroimaging features of dyssynergia cerebellaris myocionica in a Chinese family / 中华神经科杂志

Objective To investigate the clinical,genetic and neuroimaging features by reporting a family with dyssynergia cerebellaris myoclonica. Methods The proband was examined clinically by neuroimaging,electromyography ( EEG),skin and muscles pathology and hematology.The patients with the illness in the family were followed up and the pedigree was drawn.Results There were 6 patients with dyssynergia cerebellaris myoclonica of the 27 family members in the family.All patients had disproportionate myoclonus,epilepsy,progressive cerebellar ataxia performance. Proband brain MRI showed cerebral atrophy.Cerebellar and cortical atrophy were more serious than other parts.There were long T,and long T2 signals in the white matter,high signal in T2FLAIR.EEG showed bursts of spike-low wave,polyspilke-low waves and polyspike waves distributing in the whole brain.Pathology of the skin and muscles was normal.Conclusions Dyssynergia cerebellaris myoclonica is an autosomal dominant disease,characterised by myoclonus,progressive cerebellar ataxia and epilepsy.Brain MRI shows cerebral cortical and cerebellar atrophy,abnormal signal in white matter.EEG showes spike and ware wave.The diagnosis is mainly based on family history,typical clinical manifestations,brain MRI and EEG changes.

The Association of SERPINE2 Gene with COPD in a Chinese Han Population

PURPOSE: Polymorphisms of several candidate genes have been studied and associated with the development of chronic obstructive pulmonary disease (COPD). One such candidate is the SERPINE2 (Serpin peptidase inhibitor, clade E member 2) gene. MATERIALS AND METHODS: To assess whether the SERPINE2 gene is associated with COPD in a Chinese Han population. Samples were collected from a Chinese Han population and analyzed for the association of single nucleotide polymor phisms (SNPs) or haplotypes of SERPINE2 gene with COPD in a case-control study. Three SNPs including rs840088 G/A in intron 1, rs1438831 A/G in 5' upstream sequence and rs3795879 G/A in intron 3 were detected using the polymerase chain reaction (PCR)-based restriction fragment length polymorphism technique in 409 COPD subjects and 411 controls. Genotyping of the SREPINE2 polymorphisms at positions rs840088, rs1438831and rs3795879 was performed. RESULTS: We found that none of the rs840088G/A, rs1438831G/A and rs3795879 G/A polymorphisms were associated with the disease. The p-values were 0.630, 0.208 and 0.398 respectively. CONCLUSION: Our data suggested that there was no significant association between SERPINE2 polymorphism and COPD susceptibility in the Chinese Han population.

Gene mapping of a nonsyndromic hearing impairmint family / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To map the gene responsible for nonsyndromic hearing impairment in a consanguineous family.</p><p><b>METHODS</b>Firstly, X chromosome scanning was used to exclude X chromosome. Secondly, candidate gene analyzing and genome scanning were performed by homozygosity mapping. Then, additional markers flanking the tightly linked marker were tested to confirm linkage and decide the candidate region.</p><p><b>RESULTS</b>The nonsyndromic hearing impairment of this family was autosomal recessive. Twenty-five known genes were excluded. Autosomal genome scanning indicated that D17S1293 was tightly linked with disease gene. And further study mapped the disease gene to a 5.07 cM interval bounded by D17S1850 and D17S1818.</p><p><b>CONCLUSION</b>The disease gene of the family is mapped to a 5.07 cM interval between D17S1850 and D17S1818, which is a new locus of autosomal recessive nonsyndromic hearing impairment.</p>

Linkage analysis of X-linked nuclear protein gene in Smith-Fineman-Myers syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the linkage between Smith-Fineman-Myers syndrome (SFMS) and X-linked nuclear protein(XNP) locus.</p><p><b>METHODS</b>Polymerase chain reaction and denaturing polyacrylamide gel electrophoresis were used to genotype two polymorphic short tandem repeats within XNP gene.</p><p><b>RESULTS</b>One of the two short tandem repeats was informative in SFMS family from Shandong, China. Recombination between SFMS locus and XNP gene was observed in the SFMS family.</p><p><b>CONCLUSION</b>XNP gene is not associated with the disease in the SFMS family from Shandong, China. SFMS exhibits locus heterogeneity at molecular level.</p>

The C677T mutation in the methylenetetrahydrofolate reductase gene and its association with deep vein thrombophilia in Shandong Hans / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the prevalence of methylenetetrahydrofolate reductase (MTHFR) C677T genotype and its association with deep vei n thrombophilia in Chinese.</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was conducted to examine mutation with 63 deep vein thrombophilic patients and 80 health controls in Shandong Hans. The genotype frequencies were calculated by gene counting in patients and controls, and an analysis was made on the association of MTHFR C677T mutation with deep venous thrombosis in Shandong Hans.</p><p><b>RESULTS</b>In case- controls, the frequencies of C/T heterozygote were 41.27% and 43.75%; whereas those of T/T homozygote were 52.38% and 36.25%. Significantly elevated mutation was observed in patients(Chi-square=6.372, P 0.01 OR(T/T)=4.552 95% confidence interval:1.440-14.390, Chi-square =6.742 P=0.009).</p><p><b>CONCLUSION</b>The C677T mutation of methylenetetrahydrofolate reductase gene is a risk factor associated with deep vein thrombophilia in Shandong Hans.</p>

Genomic structure of low density lipoprotein receptor related protein 5 gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the genomic structure of low density lipoprotein receptor related protein 5 (LRP5) gene.</p><p><b>METHODS</b>cDNA sequence encoding LRP5 was used to screen genomic clones containing LRP5 gene by computer hybridization approach. By comparing the cDNA sequence of LRP5 with the genomic sequences, the genomic structure of LRP5 was determined, and then it was conformed by amplifying and sequencing the sequences of exons and splicing junction.</p><p><b>RESULTS</b>The genomic sequence of LRP5 gene was 131.6 kb in length, containing 23 exons and 22 introns. Three single nucleotide polymorphisms were detected within the coding sequences of LRP5 gene, namely A459G in exon 2, C2220T in exon 10 and G4416C in exon 21. Four polymorphic markers, D11S1917, D11S4087, D11S1337 and D11S4178, located in the 5' flank sequence, introns 1, 4, and 13 of the LRP5 gene, respectively.</p><p><b>CONCLUSION</b>The characterization of genomic structure of LRP5 gene allows the investigators to detect disease-causing mutation within the gene and further study the function of LRP5 gene.</p>