Exome Sequence Analysis to Characterize Undiagnosed Family Segregating Motor Impairment and Dystonia.

Background: Hypermanganesemia with dystonia 1 (HMNDYT1) is a rare genetic disorder characterized by elevated blood manganese levels. This condition is associated with polycythemia, motor neurodegeneration with extrapyramidal features, and hepatic dysfunction, which can progress to cirrhosis in some patients. Materials and Methods: In this study, a consanguineous Saudi family with two affected individuals exhibiting symptoms of severe motor impairment, spastic paraparesis, postural instability, and dystonia was studied. Clinical and radiographic evaluations were conducted on the affected individuals. Whole exome sequencing (WES) was performed to diagnose the disease and to determine the causative variant underlying the phenotype. Moreover, Sanger sequencing was used for validation and segregation analysis of the identified variant. Bioinformatics tools were utilized to predict the pathogenicity of candidate variants based on ACMG criteria. Results: Exome sequencing detected a recurrent homozygous missense variant (c.266T>C; p.L89P) in exon 1 of the SLC30A10 gene. Sanger sequencing was employed to validate the segregation of the discovered variant in all available family members. Bioinformatics tools predicted that the variant is potentially pathogenic. Moreover, conservation analysis showed that the variant is highly conserved in vertebrates. Conclusions: This study shows that exome sequencing is instrumental in diagnosing undiagnosed neurodevelopmental disorders. Moreover, this study expands the mutation spectrum of SLC30A10 in distinct populations.

Expression pattern analysis of the MAGE family genes in breast cancer patients and hypomethylation activation in the MCF-7 cells.

Melanoma antigen gene (MAGE) families are cancer-testis genes that normally show expression in the testes. However, their expressions have been linked with various types of human cancers, including BC. Therefore, the primary purposes of the present research were to assess the expression of MAGE-A, -B, and -C genes in Saudi female patients with BC and determine their regulation via the epigenetic mechanism. Ten BC samples were analyzed for the expression levels of nine MAGE-A genes, six MAGE-B genes, and three MAGE-C genes using the RT-PCR technique. All 18 evaluated genes except for MAGE-A1, -A3, -A4, and -B5 showed weak band expressions in some BC specimens. MAGE-A6 and -B2 were expressed in 40 % of the BC tissue samples, and MAGE-A9, -A10, and -B6 were expressed in 30 %. The lowest expression levels were found for MAGE-A11, -B1, -B3, -B4, -C1, and -C2 in 10 % of the BC specimens and for MAGE-A9,--B2, and --C3 in 20 % of the samples. The most frequently expressed gene was MAGE-A8 (found in 70 % of the BC samples), which suggests that it may serve as - a marker for screening of BC. In vitro treatment, the 5-aza-2'-deoxycytidine agent led to a significant rise in mRNA expressions for all tested genes related to the MAGE-A family, except for MAGE-A10. By contrast, among the genes in the MAGE-B and -C families, only MAGE-B1 and -C2 exhibited detectable mRNA expression levels after treatment.