The novel homozygous p.Asn197_Ser201del mutation in BTD gene is associated with profound biotinidase deficiency in an Iranian consanguineous family.

BACKGROUND: Biotinidase deficiency is an autosomal recessive inherited inborn error of biotin metabolism. Biotin as a water-soluble vitamin is the prosthetic group of biotin-dependent carboxylase enzymes, and by enhancing their function plays a key role in amino acid catabolism, fatty acid synthesis, and gluconeogenesis. Beyond its prosthetic group role, it has been recognized that biotin regulates the level of gene transcription in the eukaryotic cells, therefore any defect in these pathways causes a multisystem metabolic disorder characterized by neurological and cutaneous symptoms. METHODS AND RESULTS: We report the identification of a novel pathogenic variant in the BTD gene, c.528_542del15 (p.Asn197_Ser201del, UniProt P43251-1) in an Iranian consanguineous family with a severe form of the disease. The segregation analysis in the family was consistent with phenotype and the identified variant was predicated as a pathogenic mutation by the in-silico prediction tools. Computer structural modeling suggests the deleted amino acid residues are located near the biotinidase active site and disrupt the special conformations which are critical for the enzyme activity, and also N-glycosylation. CONCLUSIONS: This study further expands the mutation spectrum of the BTD gene underlying cause of profound biotinidase deficiency.

Knockdown of Sal-like 4 expression by siRNA induces apoptosis in colorectal cancer.

Colorectal cancer (CRC) is known as the third most common malignancies among men and women and is also the second leading cause of cancer-related deaths worldwide. It has been indicated that a variety of risk factors are involved in the pathogenesis of CRC. Spalt-like transcription factor 4 (SALL4) is known as a transcription factor that plays an important role in the proliferation of cancerous cells. In this study, using a specific sequence of small interfering RNA (siRNA) against the sequence of SALL4, its activity is investigated in the CRC cell line (sw742). The CRC cells (sw742) were cultured and then, using a specific anti-SALL4 siRNA, their toxic doses were determined. Then, the gene is transfected into the cell. Proliferation and expression of the SALL4 and Bcl-2 gene were measured using the real-time polymerase chain reaction method. Cell death was evaluated by propidium iodide staining and fluorescence-activated cell sorting analysis. Our results indicated that the specific concentration of siRNA of the SALL4 gene was 62.5 nmole. Gene expression of SALL4 and Bcl-2 results showed that expression of Bcl-2 gene in the siRNA group was significantly reduced. In conclusion, our finding indicated that it could be used as a therapeutic and diagnostic biomarker in the treatment of patients with CRC.