Genomics DNA Profiling in Elite Professional Soccer Players: A Pilot Study

Functional variants in exonic regions have been associated with development of cardiovascular disease, diabetes and cancer. Athletic performance can be considered a multi-factorial complex phenotype. Genomic DNA was extracted from buccal swabs of seven soccer players from the Fulham football team. Single nucleotide polymorphism (SNPs) genotyping was undertaken. To achieve optimal athletic performance, predictive genomics DNA profiling for sports performance can be used to aid in sport selection and elaboration of personalized training and nutrition programs. Predictive DNA profiling may be able to detect athletes with potential or frank injuries, or screening and selection of future athletes, and can help them to maximize utilization of their potential and improve performance in sports. The aim of this study is to provide a wide scenario of specific genomic variants that an athlete carries, to implement which measures should be taken to maximize the athlete’s potential

The genetic landscape of autism spectrum disorder in the Middle Eastern population

Introduction: Autism spectrum disorder (ASD) is characterized by aberrations in social interaction and communication associated with repetitive behaviors and interests, with strong clinical heterogeneity. Genetic factors play an important role in ASD, but about 75% of ASD cases have an undetermined genetic risk.Methods: We extensively investigated an ASD cohort made of 102 families from the Middle Eastern population of Qatar. First, we investigated the copy number variations (CNV) contribution using genome-wide SNP arrays. Next, we employed Next Generation Sequencing (NGS) to identify de novo or inherited variants contributing to the ASD etiology and its associated comorbid conditions in families with complete trios (affected child and the parents).Results: Our analysis revealed 16 CNV regions located in genomic regions implicated in ASD. The analysis of the 88 ASD cases identified 41 genes in 39 ASD subjects with de novo (n = 24) or inherited variants (n = 22). We identified three novel de novo variants in new candidate genes for ASD (DTX4, ARMC6, and B3GNT3). Also, we have identified 15 de novo variants in genes that were previously implicated in ASD or related neurodevelopmental disorders (PHF21A, WASF1, TCF20, DEAF1, MED13, CREBBP, KDM6B,SMURF1, ADNP, CACNA1G, MYT1L, KIF13B, GRIA2, CHM, and KCNK9). Additionally, we defined eight novel recessive variants (RYR2, DNAH3, TSPYL2, UPF3B KDM5C, LYST, and WNK3), four of which were X-linked.Conclusion: Despite the ASD multifactorial etiology that hinders ASD genetic risk discovery, the number of identified novel or known putative ASD genetic variants was appreciable. Nevertheless, this study represents the first comprehensive characterization of ASD genetic risk in Qatar's Middle Eastern population

Identification of novel cDNAs expressed in murine cerebellum

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A Novel Mutation of VPS33B Gene Associated with Incomplete Arthrogryposis-Renal Dysfunction-Cholestasis Phenotype

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations of the VPS33B encoding the vacuolar protein sorting 33B (VPS33B), which is involved in the intracellular protein sorting and vesicular trafficking. We report a rare case of ARC syndrome without arthrogryposis caused by a novel mutation of VPS33B. A female patient of Greek origin presented on the 14th day of life with renal tubular acidosis, Fanconi syndrome, nephrogenic diabetes insipidus, and cholestasis with normal gamma-glutamyl transpeptidase, without arthrogryposis and dysmorphic features. She was born to apparently healthy, nonconsanguineous parents. Additional features included dry and scaling skin, generalized hypotonia, hypoplastic corpus callosum, neurodevelopmental delay, failure to thrive, short stature, recurrent febrile episodes with and without infections, and gastrointestinal bleeding. DNA testing revealed that the patient was homozygous for the novel c.1098_1099delTG (p.Glu367Alafs∗17) mutation of exon 14 of VPS33B gene (NM_018668) on chromosome 15q26.1, leading to a nonsense frameshift variant of VPS33B with premature termination of translation. Her parents were heterozygous for the same VPS33B mutation. The prognosis was predictably poor in the context of the intractable polyuria necessitating long-term parenteral fluid administration via indwelling central catheter leading to catheter-related sepsis, to which she eventually succumbed at the age of 7 months. This is the first published VPS33B mutation in an ARC patient of Greek origin. The current case adds to the spectrum of ARC-associated VPS33B mutations and provides evidence supporting the existence of incomplete ARC phenotype. Increased awareness and early genetic testing for ARC are suggested in cases with isolated cholestasis and/or renal tubular dysfunction, even in the absence of arthrogryposis

Mutations in zinc finger 407 [ZNF407] cause a unique autosomal recessive cognitive impairment syndrome

International audienceA consanguineous Arab family is affected by an apparently novel autosomal recessive disorder characterized by cognitive impairment, failure-to-thrive, hypotonia and dysmorphic features including bilateral ptosis and epicanthic folds, synophrys, midface hypoplasia, downturned mouth corners, thin upper vermillion border and prominent ears, bilateral 5th finger camptodactyly, bilateral short 4th metatarsal bones, and limited knee mobility bilaterally

A Novel Missense Mutation in Causes Congenital Disorder of Glycosylation Type I (Cerebello-Ocular Syndrome)

A consanguineous Qatari family having an autosomal recessive disorder characterized by severe mental retardation, cerebellar vermis hypoplasia, retinal degeneration, optic nerve atrophy, ataxic gait, and seizures was studied for identification of the offending gene and mutation. Homozygosity mapping identified an 11.4 Mb critical interval at 4q12 to q13.2 that would contain the gene responsible for the disorder. Ten positional candidate genes were screened for pathogenic mutations, but none were identified. Next-generation exome sequencing in one affected individual identified a novel SRD5A3 missense mutation c.T744G/p.F248L, which was subsequently confirmed by Sanger sequencing, suggesting a congenital disorder of glycosylation type IQ defect. Isoelectric focusing of serum transferrin showed a type I pattern indicative of an N -glycan assembly defect. This is a novel pathogenic mutation and the first SRD5A3 missense mutation as all others are protein-truncating mutations