Journal of Clinical & Medical Genomics

De Barsy syndrome is a rare autosomal recessive genetic disorder characterized by growth retardation, intellectual disability, a prematurely-aged appearance (progeroid features) and loose skin (cutis laxa) as well as eye abnormalities and others. Some cases of de Barsy syndrome have been linked with mutations PYCR1 or ALDH18A1. We describe a family with two siblings with clinically severe de Barsy syndrome in whom two novel mutations in ALDH18A1 (p.Glu100* and p.Arg724His) were found by clinical exome sequencing using TruSight One panel. The p.Glu100* is a novel mutation predicted to cause absence of the protein. The p.Arg724His has been found with low frequency (0.000016) but not in association with human disease; it has been scored as pathogenic by CADD, MetaSVM, Polyphen2, MutationAssessor, SIFT and MutationTaster. The level of ammonia in serum was determined in second sibling and was in normal range. Amino acid profile in serum revealed decreased concentration of arginine, cytruline, homocysteine, PHE and ornithine. The patients suffer from severe symptoms of GERD such as vomiting, feeding problems instead of multistage therapy including Nissen fundoplication procedure as well as from epilepsy requires complex multidrug therapy. L-Arginine (200 mg/kg) and citrulline (100 mg/kg) were supplemented in the second sibling. The disease leads to premature apoptosis, so antioxidants (coenzyme Q, vitamin A and E) as well as carnitine were supplemented but without spectacular clinical results.

We provide clinical description of severe phenotype of de Barsy syndrome. Our molecular report broadens the spectrum of ALDH18A1 mutations causing de Barsy syndrome.

Next-generation sequencing (NGS) technologies including DNA sequencing and RNA sequencing provide “omics” approaches to reveal genomic, transcriptomic, and epigenomic landscapes of individual cancers. A variety of genomic aberrations can be screened simultaneously, such as common and rare variants, structural variations (e.g. insertions and deletions), copy-number variation, and fusion transcripts. NGS technologies together with bioinformatics analysis, which expand our knowledge, are increasingly used to simultaneously analyze multiple genes in a cost and time-effective manner and have been applied in analyzing clinical cancer samples and offering NGS-based molecular diagnosis. Therefore, NGS is increasingly valuable as a tool for diagnosis for a number of cancers. Here we briefly introduce NGS technologies and summarize the recent applications in cancer research and molecular diagnosis in breast and prostate cancers.

Background: RsaI/PstI and DraI polymorphisms of cytochrome P450 2E1 (CYP2E1) gene are regarded as the most common polymorphisms associated with gastric cancer (GC). Very few data of these polymorphisms have been reported from India with regard to GC risk. We evaluated RsaI: -C1053T (rs2031920), PstI: -G1295C (rs3813867) site in the 5’ flanking region, DraI: T7668A (rs6413432) site in intron 6, -G71T rs6413420 and G4768A or V179I rs6413419 polymorphisms of CYP2E1 with GC risk in the population of West Bengal, India.

Methods: We enrolled 105 GC patients (cases) and corresponding sex, age and ethnicity matched normal 108 individuals (controls) for the study. Genotyping for rs6413419, rs6413420, rs6413432, rs2031920, rs3813867 of CYP2E1 was performed using DNA sequencing and RFLP analysis.

Results and conclusion: Our results suggest that the difference between genotype frequencies of rs3813867 and rs2031920, although not statistically significant but the allele frequencies of rs3813867 (OR=2.29, 95% CI=1.01-5.18, p=0.042) and rs2031920 (OR=2.29, 95% CI=1.01-5.18, p=0.042) showed significant difference between GC and control individuals. This when pooled with smoking augmented GC risk by nearly 4-fold. Therefore, a larger population is needed to be screened to confirm the association of these studied SNPs with GC in India.