X-linked intellectual disability (XLID) is a heterogeneous condition associated with mutations in >100 genes, accounting for over 10% of all cases of intellectual impairment. The majority of XLID cases show nonsyndromic forms (NSXLID), in which intellectual disability is the sole clinically consistent manifestation. Here we performed X chromosome exome (X-exome) sequencing to identify the causative mutation in an NSXLID family with four affected male siblings and five unaffected female siblings. The X-exome sequencing at 88× coverage in one affected male sibling revealed a novel missense mutation (p.Tyr1074Cys) in the asparagine-linked glycosylation 13 homolog (ALG13) gene. Segregation analysis by Sanger sequencing showed that the all affected siblings were hemizygous and the mother was heterozygous for the mutation. Recently, a de novo missense mutation in ALG13 has been reported in a patient with X-linked congenital disorders of glycosylation type I. Our study reports the first case of NSXLID caused by a mutation in ALG13 involved in protein N-glycosylation.

Seoul-t'ukpyolsi, Republic of Korea Here we investigated effects of anacardic acid (AA) on the regulation of lipogenesis in differentiated human adipocytes, and elucidated possible epigenetic mechanisms via p300 histone acetyltransferase activity. To investigate the role of histone acetylation in lipogenesis regulation, we evaluated triglyceride (TG) contents, expression of key lipogenic enzyme acetyl-CoA carboxylase (ACC) and sterol regulatory element binding protein 1c (SREBP-1c) in primary cultured adipocytes isolated from subcutaneous adipose tissues. Treatment of AA or knockdown of p300 by using transient transfection of p300 siRNA led to significant reduction of TG contents, SREBP-1c and ACC expression, indicating that p300 mediates SREBP-1, ACC expression, and corollary lipid production. While p300 overexpression by p300WT was associated with significantly enhanced activity of SREBP1-908luc promoter, the SREBP1-908luc promoter activity was significantly reduced in the presence of p300DHAT. In addition, we performed a promoter assay using HEK293T cells treated with AA or TSA. While the SREBP1-908luc promoter activity was significantly decreased by AA, but significantly increased by TSA treatment. These findings suggest that histone acetyltransferase activity of p300, not a p300 expression per se, is critical for the transcriptional regulation of SREBP-1 and p300HAT inhibitors such as AA could be employed as anti-obesity modalities.

Background: Preclinical studies of mesenchymal stem cells in various animal models demonstrate accelerated wound healing through a variety of mechanisms. The aim of this small-scale study was to evaluate the effectiveness of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in the treatment of patients with venous ulcers. Study design and method: A randomized, double-blind, placebo-controlled evaluation was selected to protect against bias. A total of 11 patients were randomly assigned to one of three groups: Group A (n¼4) received conventional standard therapy and control saline spray, group B (n¼3) received conventional standard therapy and fibrin spray, and group C (n¼4) received conventional standard therapy and BM-MSCs topically delivered using a fibrin spray. The total duration of the treatment was 24 weeks or earlier if the wound is completely closed. Patients were evaluated clinically at baseline and every 4 weeks up to week 24. The primary efficacy endpoint of the study is increased wound closure (cm/wk). Healing rates were calculated using the Gilman's method. Data were analyzed by comparing the mean healing rates among treatment groups. Results: The average healing rate at week-4 for groups A, B, and C was 0.0006, -0.0522, and 0.1082 cm/wk, respectively. Patients received BM-MSCs treatment (Group C) showed higher mean healing rates and a significant reduction in wound size when compared to groups A and B at all evaluation time points. No adverse events were reported. Conclusions: This pilot study shows that topical application of autologous BM-MSCs may be an effective modality to promote healing in patients with difficult-to-heal wounds. However, larger studies are needed to confirm this finding.