Molecular Genetics & Genomic Medicine

BACKGROUND: Cancer genes tend to be highly mutated under positive selection. Better understanding the recurrently mutated genes (RMGs) in cancer is critical for explicating the mechanisms of tumorigenesis and providing vital clues for therapy. Although some studies have investigated functional impacts of RMGs in specific cancer types, a comprehensive analysis of RMGs and their mutational impacts across cancers is still needed. METHODS: We obtained data from The Cancer Genome Atlas (TCGA) and calculated mutation rate of each gene in 31 cancer types...

BACKGROUND: Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is the second most common cause of primary amenorrhea and characterized by absence of the uterus and the upper part of the vagina. The etiology of MRKH is mainly unknown but a contribution of genomic alterations is probable. A molecular disturbance so far neglected in MRKH research is aberrant methylation at imprinted loci. In fact, MRKH has been reported in patients with the imprinting disorder Silver-Russell syndrome. METHODS: We report on a rare patient with MRKH and SRS due to an ICR1 hypomethylation in 11p15...

BACKGROUND: We aimed to provide a set of previously reported PAH-associated missense and nonsense variants, and evaluate the pathogenicity of those variants. METHODS: The Human Gene Mutation Database, PubMed, and Google Scholar were searched for previously reported PAH-associated genes and variants. Thereafter, both exome sequencing project and exome aggregation consortium as background population searched for previously reported PAH-associated missense and nonsense variants...

Dentistry constitutes the basic nucleus of professionals of higher level of health in Brazil with one of the largest concentrations of dentists per capita in the world. However, the genetic in dentistry in Brazil is explored, basically, in research field. Future actions need to be performed in order to deep the whole knowledge about diagnosis and treatment of diseases with genetic basis in dentistry, in Brazil.

A historical summary of genetics and genomic medicine in Argentina. We go through the achievements and difficulties in the implementation of genetic and genomic services both in academia and health care.

BACKGROUND: When a family encounters the loss of a child early in life, extensive genetic testing of the affected neonate is sometimes not performed or not possible. However, the increasing availability of genomic sequencing may allow for direct application to families in cases where there is a condition inherited from parental gene(s). When neonatal testing is not possible, it is feasible to perform family testing as long as there is optimal interpretation of the genomic information...

BACKGROUND: Glutathione S-transferase pi 1 (GSTP1) is a cytosolic detoxifying enzyme that protects cells against deleterious effects of oxidative stress. Deregulated expression of GSTP1 protein and aberrant promoter methylation of GSTP1 gene were reported in various human tumors and were shown to be involved in the molecular pathway for cancer development. AIMS AND METHODS: In this study, we aimed to determine the expression status of GSTP1 in relation to its gene promoter methylation in Moroccan population of 30 bladder cancer (BC) patients and in two noncancerous bladder tissues used as controls...

BACKGROUND: Although the process of reclassification of a variant of uncertain significance can be complex, they are commonly detected through molecular testing. It often takes years before enough clinical data are acquired, and it can be costly and time-consuming to perform functional analysis of a single variant. It is important that other tools are developed to aid in clarifying how a specific genetic variant impacts a protein's function, and ultimately the health of the patient. METHODS: Two more newly characterized, suspected pathogenic variants in NBN and PTEN were analyzed through personalized protein modeling...

BACKGROUND: Mutations in the Janus Kinase 3 (JAK3) gene cause an autosomal recessive form of severe combined immunodeficiency (SCID) usually characterized by the absence of both T and NK cells, but preserved numbers of B lymphocytes (T-B+NK-SCID). The detection of larger (>100 bp) genomic duplications or deletions can be more difficult to be detected by PCR-based methods or standard NGS protocols, and a broad range of mutation detection techniques are necessary. METHODS: We report four unrelated Italian patients (two females and two males) with SCID phenotype...

BACKGROUND: The frequency of HLA-DQ2 and DQ8 predisposing genotypes for celiac disease (CD) has shown significant variation among different world regions and has not been previously determined among the highly interbred Brazilian population. The aim of this study was to investigate the frequency of these genotypes among Brazilian newborns (NB). METHODS: We typed DQA1*05 - DQB1*02 (DQ2.5) and DQA1*03 - DQB1*03:02 (DQ8) alleles in 329 NB using qPCR technique. Subsequently we confirmed our results by PCR-SSP using a reference kit which further identified DQ2...

BACKGROUND: Large, multigenic deletions at chromosome 7q11.23 result in a highly penetrant constellation of physical and behavioral symptoms known as Williams-Beuren syndrome (WS). Of particular interest is the unusual social-cognitive profile evidenced by deficits in social cognition and communication reminiscent of autism spectrum disorders (ASD) that are juxtaposed with normal or even relatively enhanced social motivation. Interestingly, duplications in the same region also result in ASD-like phenotypes as well as social phobias...

BACKGROUND: Prader-Willi syndrome (PWS) is a multisystem genetic disorder characterized by lack of satiety leading to morbid obesity, variable degrees of mental retardation, behavior disorders, short stature, and hypogonadism. The underlying genetic cause for PWS is an imprinting defect resulting from a lack of expression of several paternally inherited genes embedded within the 15q11.2-q13 region. Although the clinical expression of hypogonadism in PWS is variable, there are no known cases of fertility in PWS men...

BACKGROUND: One of the defining moments of human life occurs early during embryonic development, when individuals sexually differentiate into either male or female. Perturbation of this process can lead to disorders/differences of sex development (DSD). Chromobox protein homolog 2 (CBX2) has two distinct isoforms, CBX2.1 and CBX2.2: the role of CBX2.1 in DSD has been previously established, yet to date the function of the smaller isoform CBX2.2 remains unknown. METHODS: The genomic DNA of two 46,XY DSD patients was analysed using whole exome sequencing...

BACKGROUND: Human norovirus is the leading cause of acute gastroenteritis worldwide. However, in vitro culture system is complicated for human norovirus. Sequence analysis became more useful for norovirus research, particularly when using complete genomic sequences. METHODS: Real-time RT-PCR (qPCR) was performed for norovirus detection. Three modified paris of PCR primes were designed based on the alignment of the novel GII.17 norovirus complete sequence available in Genbank...

BACKGROUND: Long noncoding RNAs (lncRNAs) play important roles in carcinogenesis. However, the roles of metabolism-associated lncRNAs in cancers are still unclear. METHODS: A microarray of metabolism-associated lncRNAs was used to detect their expression patterns between gastric cancer and paired nontumorous tissues. Its results and gastric cancer differential gene expression data from public databases were used to screen the metabolic pathway-associated lncRNAs...

BACKGROUND: We examined the association of three known genome-wide association study loci for blood lipids that have lead traits for triglycerides with hypertension in the Tampere adult population cardiovascular risk study. METHODS: A Finnish cohort of 190 men with diagnosed hypertension and 279 controls were analyzed. Samples were genotyped for low-density lipoprotein receptor-related protein 1 rs11613352 (C>T), angiopoietin-like 3 rs2131925 (T>G), and fatty acid desaturase 1 rs174546 (C>T) polymorphisms using competitive allele-specific polymerase chain reaction technique...

BACKGROUND: Glycosylphosphatidylinositol (GPI) anchoring is a special type of protein posttranslational modification, by which proteins with diverse function are attached to cell membrane through a covalent linkage between the protein and the glycolipid. Phosphatidylinositol glycan anchor biosynthesis class A (PIGA) is a key enzyme in GPI anchor biosynthesis, somatic mutations or genetic variants of which have been associated with paroxysmal nocturnal hemoglobinuria (PNH), or PIGA deficiency, respectively...

BACKGROUND: Intellectual disability (ID) and dementia reflect disturbed cortical function during and after developmental age, respectively. Due to the wide heterogeneity of ID population the decline in cognitive and adaptive skills may be different in distinct genetic subgroups. METHODS: Using the British Present Psychiatric State-learning Disabilities assessment (PPS-LD) questionnaire the dementia signs were screened in 62, 22 and 44 individuals (> 35 year of age) with Down (DS, OMIM number 190685), Williams (WS, OMIM number, 194050), and Fragile X syndrome (FXS, OMIM number 309550), respectively...

BACKGROUND: Historically, groups that are most susceptible to health and healthcare disparities have been underrepresented in medical research. It is imperative to explore approaches that can facilitate the recruitment of underrepresented individuals into research studies. METHODS: Two approaches, hospital and community-based recruitment (CBR), were developed and implemented over 36 months to study the genetics of hereditary breast cancer and associated cancers in Alabama, a medically underserved state with double the national percentage of self-identifying African Americans, establishing the Alabama Hereditary Cancer Cohort...

BACKGROUND: Access to clinical diagnostic genome-wide sequencing (GWS; exome or whole genome sequencing) is limited in British Columbia. The establishment of a translational research initiative (CAUSES) to provide diagnostic genome-wide sequencing for 500 children necessitated the development of a genomic consultation service, a clinical service established to provide consultation for physicians considering GWS for their pediatric patients throughout British Columbia. The Genomic Consultation Service provides patient-specific genomic advice that may include: GWS, multi-gene panel, single gene test, referral to medical genetics for clinical evaluation, or no genetic testing...