A novel heterozygous variant of the SALL1 gene with atypical Townes-Brocks syndrome phenotypes in Chinese family.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

The pulse light mode enhances the effect of photobiomodulation on B16F10 melanoma cells through autophagy pathway.

Photobiomodulation (PBM) is the use of low irradiance light of specific wavelengths to generate physiological changes and therapeutic effects. However, there are few studies on the effects of PBM of different LED light modes on cells. Here, we investigated the difference of influence between continuous wave (CW) and pulse-PBM on B16F10 melanoma cells. Our results suggested that the pulse mode had a more significant PBM than the CW mode on B16F10 melanoma cells. Our study confirmed that ROS and Ca2+ levels in B16F10 melanoma cells treated with pulse-PBM were significantly higher than those in the control and CW-PBM groups. One mechanism that causes the difference in CW and pulse-PBM action is that pulse-PBM activates autophagy of melanoma cells through the ROS/OPN3/Ca2+ signaling pathway, and excessive autophagy activation inhibits proliferation and apoptosis of melanoma cells. Autophagy may be one of the reasons for the difference between pulse- and CW-PBM on melanoma cells. More importantly, melanoma cells responded to brief PBM pulses by increasing intracellular Ca2+ levels.

A novel compound heterozygous variant of the SLC12A3 gene in Gitelman syndrome with diabetes and the choices of the appropriate hypoglycemic drugs: a case report.

BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by mutations of the SLC12A3 gene. It is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. It is universally known that both hypokalemia and hypomagnesemia can influence insulin secretion and insulin resistance, but the exact mechanisms require further study. We identified a novel deletion variant of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes. CASE PRESENTATION: A 55-year-old diabetic female patient was hospitalized for evaluation because of paroxysmal general weakness and numbness of extremities for one year. We suspected that she was suffering from GS by initial estimation. Direct Sanger sequencing was used to analyze the causative gene SLC12A3 of GS. Oral glucose tolerance test (OGTT) was carried out to assess the glucose metabolism and insulin resistance status. Genetic analysis revealed that she was a compound heterozygote for a recurrent missense mutation c.179C > T and a novel deletion c.1740delC in SLC12A3, thus her diagnosis of GS was confirmed. The patient was treated with potassium chloride (3.0 g/d) and magnesium chloride (element magnesium 350 mg/d) on the basis of initial treatment of diabetes with hypoglycemic drug (Repaglinide, 3.0 mg/day). However, she developed frequent hypoglycemia after one week. OGTT showed that her glucose metabolism and insulin resistance much improved after potassium and magnesium supplemental therapy. Then we changed the hypoglycemic agent to a dipeptidyl peptidase-4 (DPP-4) inhibitor (Trajenta 5 mg/d), since then her blood glucose level remained normal during two-year of follow-up. CONCLUSION: We have identified a novel deletion of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes. We suggested that attention need to be paid to blood glucose monitoring in GS patients, especially when hypokalemia and hypomagnesemia are corrected. Besides, the insufficient blood volume and serum electrolyte disturbance should also be taken into consideration in the selecting hypoglycemic drugs for GS patients.