Exome sequencing identified a novel HIST1H1E heterozygous protein-truncating variant in a 6-month-old male patient with Rahman syndrome: A case report.

Rahman syndrome is a rare congenital anomaly syndrome recently described, which results from pathogenic variants in the HIST1H1E gene. The condition is characterized by variable somatic overgrowth, macrocephaly, distinctive facial features, intellectual disability, and behavioral problems. This report extends the genotype and clinical phenotype of HIST1H1E-associated Rahman syndrome.

Clinical Impact and Cost-Effectiveness of Whole Exome Sequencing as a Diagnostic Tool: A Pediatric Center's Experience.

Background: There are limited reports of the use of whole exome sequencing (WES) as a clinical diagnostic tool. Moreover, there are no reports addressing the cost burden associated with genetic tests performed prior to WES.

Objective: We demonstrate the performance characteristics of WES in a pediatric setting by describing our patient cohort, calculating the diagnostic yield, and detailing the patients for whom clinical management was altered.

Finding missing heritability in less significant Loci and allelic heterogeneity: genetic variation in human height.

Genome-wide association studies (GWAS) have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of 'missing' heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus.

Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia.

A genome-wide association study of serum uric acid (SUA) laevels was performed in a relatively isolated population of European descent from an island of the Adriatic coast of Croatia. The study sample included 532 unrelated and 768 related individuals from 235 pedigrees. Inflation due to relatedness was controlled by using genomic control.

Extent of height variability explained by known height-associated genetic variants in an isolated population of the Adriatic coast of Croatia.

Background: Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2∼10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia.

Replication of genetic variants from genome-wide association studies with metabolic traits in an island population of the Adriatic coast of Croatia.

Twenty-two single-nucleotide polymorphisms (SNPs) in 10 gene regions previously identified in obesity and type 2 diabetes (T2D) genome-wide association studies (GWAS) were evaluated for association with metabolic traits in a sample from an island population of European descent. We performed a population-based study using 18 anthropometric and biochemical traits considered as continuous variables in a sample of 843 unrelated subjects (360 men and 483 women) aged 18-80 years old from the island of Hvar on the eastern Adriatic coast of Croatia. All eight GWAS SNPs in FTO were significantly associated with weight, body mass index, waist circumference and hip circumference; 20 of the 32 nominal P-values remained significant after permutation testing for multiple corrections.

The relationship between smoking and replicated sequence variants on chromosomes 8 and 9 with familial intracranial aneurysm.

Background And Purpose: The purpose of this study was to replicate the previous association of single nucleotide polymorphisms (SNPs) with risk of intracranial aneurysm (IA) and to examine the relationship of smoking with these variants and the risk of IA.

Methods: White probands with an IA from families with multiple affected members were identified by 26 clinical centers located throughout North America, New Zealand, and Australia. White control subjects free of stroke and IA were selected by random digit dialing from the Greater Cincinnati population.

Applying novel genome-wide linkage strategies to search for loci influencing type 2 diabetes and adult height in American Samoa.

Type 2 diabetes mellitus (T2DM) is a common complex phenotype that by the year 2010 is predicted to affect 221 million people globally. In the present study we performed a genome-wide linkage scan using the allele-sharing statistic Sall implemented in Allegro and a novel two-dimensional genome-wide strategy implemented in Merloc that searches for pairwise interaction between genetic markers located on different chromosomes linked to T2DM. In addition, we used a robust score statistic from the newly developed QTL-ALL software to search for linkage to variation in adult height.

A genome-wide linkage scan identifies multiple chromosomal regions influencing serum lipid levels in the population on the Samoan islands.

Abnormal lipid levels are important risk factors for cardiovascular diseases. We conducted genome-wide variance component linkage analyses to search for loci influencing total cholesterol (TC), LDL, HDL and triglyceride in families residing in American Samoa and Samoa as well as in a combined sample from the two polities. We adjusted the traits for a number of environmental covariates, such as smoking, alcohol consumption, physical activity, and material lifestyle.