ARHGAP4 mutated in a Chinese intellectually challenged family.

OBJECTIVE: Mental retardation is characterized by lower intelligence compared to the average intelligence of persons the same age. These patients have low adaptive capacity acquired by society. The genetic factors of causing MR include monogenic disease, chromosome structural aberration, and chromosome number aberration and so on. We explored the cause of a Chinese family suffering from mental retardation. METHODS: We used karyotyping technology to determine the karyotype of the proband, and we used FISH to verify the result of the karyotyping. We used whole-exome sequencing to identify the disease-causing gene and used Sanger sequencing to verify the result of whole-exome sequencing to assess the family's gene expression. RESULTS: The G-banding of the karyotype revealed that the patient's karyotype is 46, XY. FISH revealed that the patient does not have a trisomy syndrome. The karyotype of the proband is normal. Using whole-exome sequencing, we identified 108,767 variants in the exome gene of the patient, including 101,787 SNPs and 6980 InDels. Combining clinical information and bioinformatics analysis, including databases filtering and SIFT analysis, we found ARHGAP4 in X chromosome was candidate MR disease-causing gene. PCR and Sanger sequencing results were consistent with whole-exome sequencing. ARHGAP4 (T491M) mutation was present in the genome of the proband and his mother is a carrier, while his father, sister, and brother do not carry this mutation. CONCLUSION: According to clinical information, whole-exome sequencing results and Sanger verification results, ARHGAP4 (T491M) mutation may be disease-causing gene of the MR patient. The relation between ARHGAP4 mutation and MR clinical characteristic is needed to be illuminated with participation of more MR patients.

Genome-wide analysis of 5-hmC in the peripheral blood of systemic lupus erythematosus patients using an hMeDIP-chip.

Systemic lupus erythematosus (SLE) is a chronic, potentially fatal systemic autoimmune disease characterized by the production of autoantibodies against a wide range of self-antigens. To investigate the role of the 5-hmC DNA modification with regard to the onset of SLE, we compared the levels 5-hmC between SLE patients and normal controls. Whole blood was obtained from patients, and genomic DNA was extracted. Using the hMeDIP-chip analysis and validation by quantitative RT-PCR (RT-qPCR), we identified the differentially hydroxymethylated regions that are associated with SLE. There were 1,701 genes with significantly different 5-hmC levels at the promoter region in the SLE patients compared with the normal controls. The CpG islands of 3,826 genes showed significantly different 5-hmC levels in the SLE patients compared with the normal controls. Out of the differentially hydroxymethylated genes, three were selected for validation, including TREX1, CDKN1A and CDKN1B. The hydroxymethylation levels of the three genes were confirmed by RT-qPCR. The results suggested that there were significant alterations of 5-hmC in SLE patients. Thus, these differentially hydroxymethylated genes may contribute to the pathogenesis of SLE. These findings show the significance of 5-hmC as a potential biomarker or promising target for epigenetic-based SLE therapies.