Association of PTPN22 gene polymorphism with type 1 diabetes mellitus in Chinese children and adolescents.

Previous studies have indicated that the protein tyrosine phosphatase nonreceptor type 22 gene (PTPN22) is associated with type 1 diabetes (T1DM) in the Caucasian population. In the present study, we investigated the relationship between PTPN22 genetic polymorphisms and T1DM in Chinese children. A total of 202 children and adolescents with T1DM and 240 healthy control subjects of Chinese Han origin were included in our analysis. Polymerase chain reaction-restriction fragment length polymorphism was used to determine the presence of the C1858T polymorphism in the PTPN22 gene. We found that the TT +TC genotype and the T allele of C1858T were more frequent in T1DM patients (19.40 and 10.0%, respectively) than in healthy subjects (7.51 and 4.0%, respectively), and the difference was significant (both P < 0.001). After adjusting for confounding variables such as gender, age, and family history of T1DM, the difference remained significant (P = 0.007, odds ratio = 2.88, 95% confidence interval 1.76-4.32). Our results indicate that genetic polymorphisms in the PTPN22 gene may increase the risk of T1DM in Chinese children and adolescents.

Mutation screening of TSC1 and TSC2 genes in Chinese Han children with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder caused by mutations in the TSC1 or TSC2 genes and is frequently associated with hamartoma formation in multiple organ systems. Here, we report two novel mutations in the TSC2 gene, including a splicing mutation (IVS 29 +1G>C) in intron 29 and a deletion/insertion mutation (C.5090-5092delCCA- inAG) in exon 39 in two Chinese Han children with TSC whose first clinical manifestation was seizure. The identification of these two mutations confirmed the diagnosis of TSC and expands the spectrum of TSC2 mutations causing TSC.

A novel TSC1 mutation (c.1964delA) in a Chinese patient with tuberous sclerosis complex.

Tuberous sclerosis complex is an autosomal-dominant heritable disease caused by mutations in the TSC1 and TSC2 genes. We studied a Chinese patient with sporadic tuberous sclerosis complex. The clinical features of this patient included epilepsy, hypomelanotic macules and angiofibromas on his back; a cranial CT scan showed subependymal nodules along the lateral walls of the lateral ventricles. The TSC1 and TSC2 genes were studied by PCR and direct sequencing of the entire coding region and exon-intron boundaries of these genes. A novel deletion mutation (c.1964delA) in the TSC1 gene exon 15 was identified, which was not present in his parents or 100 unrelated normal controls. This is the first report of this c.1964delA mutation of the TSC1 gene, associated with tuberous sclerosis complex, expanding the spectrum of TSC1 mutations that cause this disease.

A novel RUNX2 mutation (T420I) in Chinese patients with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal-dominant heritable skeletal disease caused by heterozygous mutations in the RUNX2 gene. We studied a Chinese family that included three affected individuals with CCD phenotypes; the clinical features of patients with CCD include delayed closure of fontanelles, frontal bossing, dysplasia of clavicles, late tooth eruption, and other skeletal anomalies. X-ray analysis showed aplasia of the clavicles. The RUNX2 gene was studied by PCR and direct sequencing of the entire coding region and the exon-intron boundaries of the gene. A novel missense mutation (c.1259C-->T[p.T420I]) in RUNX2 gene exon 7 was identified; it was found in the affected individuals in this Chinese family, but was not present in an unaffected family member or in 100 unrelated normal controls. This is the first report that gives evidence that the T420I mutation of RUNX2 is associated with CCD, expanding the spectrum of RUNX2 mutations causing CCD.