Mutations in LTBP3 cause acromicric dysplasia and geleophysic dysplasia

Acromicric dysplasia and geleophysic dysplasia are both forms of acromelic dysplasia.  Several causative genes have been identified for the acromelic dysplasias, all of which affect TGF-β signalling and/or interactions with fibrillin.  Here, we have used massive parallel sequencing to identify a dominant mutation in latent TGF-β binding protein-3 (LTBP3) in a family with acromicric dysplasia, […]

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Naturally occurring BRCA2 alternate mRNA splicing events in clinically relevant samples

Genetic testing of BRCA1 and BRCA2 genes in cancer patients frequently reveals gene variations with unknown clinical effects.  Some of these variations might affect mRNA splicing, an important step in gene expression.  Aberrant splicing is typically determined by looking for novel mRNA molecules.  We wanted to know if these molecules could also occur at random.  […]

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Germline RRAS2 Mutations are not associated with Noonan Syndrome

Mutations in a variety of Ras-MAPK pathway genes are detected in 70-80% of patients with Noonan Syndrome (NS) and related disorders, collectively referred to as RASopathies. Certain patients with RASopathies are predisposed to developing juvenile myelomonocytic leukemia (JMML), a myeloproliferative disorder of early childhood. We recently identified somatic mutations in RRAS2 in JMML and hypothesized […]

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Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies. These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional […]

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Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations

Newer genetic counselling approaches are needed to test large populations for cancer gene alterations. We compared traditional face-to-face counselling with a DVD assisted approach. This randomised study was undertaken in the London Jewish population while testing for BRCA gene alterations. We found DVD assisted counselling was not inferior to traditional face-to-face counselling for increase in […]

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AKAP2 identified as a novel gene mutated in a Chinese family with adolescent idiopathic scoliosis

Adolescent idiopathic scoliosis (AIS) is a common spinal deformities found in adolescent populations, while Mendelian-inherited family cases are quite rare. An autosomal-dominant inherited AIS family has been investigated and one missense mutation harbored in AKAP2 gene was found. The AKAP2 gene is located in a previously reported linkage locus (IS4) on chromosome 9q31.2-q34.2, which could […]

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Risky Business: Getting a Grip on BRIP

BRIP1 has been implicated in hereditary breast cancer due to its role in DNA repair and cell-cycle control. BRIP1 was first associated with breast cancer in 2006, when a study of 1,212 familial breast cancer cases and 2,081 controls reported a significant two-fold increased risk. Many commercial laboratories include this gene on breast cancer susceptibility […]

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Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel

Cystic kidney disease is an inherited condition that can present before birth, using antenatal ultrasound scanning. The finding of cystic kidney disease is important as it can be associated with other developmental problems affecting the brain, heart and skeleton. The genetic changes underlying cystic kidney disease are numerous. Here we have used a panel of […]

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