Pulmonary arterial hypertension (PAH) in children is a progressive and often fatal disease of the lung vessels, for which no curative therapy exists. PAH may be heritable: mutations in the BMPR2-gene have been found in about 15% of children with the disease. In a national cohort of Dutch children with unexplained PAH, we identified mutations […]
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Troponin activator augments muscle force in nemaline myopathy patients with nebulin mutations
Nemaline myopathy (NM) is the most common non-dystrophic congenital myopathy and is most frequently caused by mutations in the nebulin gene. The sarcomeric protein nebulin plays a crucial role in skeletal muscle performance. NM patients with nebulin mutations have muscle weakness through mechanisms including a lower responsiveness to calcium. No therapy exists to treat muscle […]
Rhizomelic chondrodysplasia punctata and cardiac pathology
Rhizomelic Chondrodysplasia Punctata (RCDP) is a rare genetic disorder associated with symmetrical shortening of the upper arms and legs, contractures, cataracts and developmenatal delay. The levels of plasmalogens (major constituents of cellular membranes) are low. Although high levels of plasmalogens are normally found in the heart, heart abnormalities have not previously been strongly associated with […]
Meta-Analysis of Genome-Wide Studies Identifies MEF2C SNPs Associated with Bone Mineral Density at Forearm
This paper finds different variants in MEF2C are associated with forearm bone mineral density (BMD) compared to the MEF2C variants associated with femoral neck BMD. We conclude that these variants are likely independent signals that have different independent effects on the two BMD phenotypes. It is also possible that both associations arise from several rare […]
A new seipin-associated neurodegenerative syndrome
Seipin is a protein encoded by BSCL2 gene. BSCL2 mutations can produce congenital generalized lipodystrophy (Berardinelli-Seip syndrome). We have discovered that a novel BSCL2 mutation, c.985C>T, is responsible of a new severe degenerative brain disease, leading to death before age 9. This mutation causes an alternative splicing site leading to the skipping of BSCL2 exon […]
Impact of direct-to-consumer genomic testing at long term follow-up
There are few empirical data to inform the use and regulation of direct-to-consumer (DTC) genome-wide disease risk tests. The Scripps Genomic Health Initiative is a prospective longitudinal cohort study that aims to determine the psychological, behavioral, and clinical impacts of genomic testing for common disease susceptibility. Our findings at one-year follow-up indicate that over a […]
Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic kidney disease in Japanese individuals by a genome-wide association study
We performed a genome-wide association study to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in Japanese. The rs9846911 at 3q28 was significantly associated with CKD in Japanese. The rs2074381 and rs2074380 of ALPK1 at 4q25 were also significantly associated with CKD in individuals with diabetes mellitus. Combined genotype analysis of these […]
Ovarian cancer among 8005 women from a breast cancer family history clinic: No increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2
Families with mutations in BRCA1/BRCA2 genes have a high-risk of both breast and ovarian cancer. We examined whether there was increased ovarian cancer risk in families which were untested or tested negative for BRCA1/2 mutations. By performing person-years at risk analyses on 8005 women from 895 families we found there to be no increased risk […]
Recent Advances in the Genetics of Sarcoidosis
Sarcoidosis is a systemic granulomatous disorder most commonly affecting the lung. While we do not know its cause/s, there is compelling evidence that a genetic predisposition to developing the disease exists. However, sarcoidosis is not a single-gene disorder; instead, it is likely to result from a complex interplay of multiple genes and environmental factors. The […]
Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci
The Mexican population has an increased susceptibility to dyslipidemias predisposing to coronary heart disease. We performed the first Mexican GWAS for lipids in which we observed a novel locus for high triglycerides near the NPC1 gene. Using cross-ethnic mapping we also restricted several GWAS loci shared between Mexicans and Europeans. At the APOA5 locus, we […]