C9orf72 and intracerebral hemorrhage.

The chromosome 9 open reading frame 72 (C9orf72) GGGGCC repeat expansion has been associated with several diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. It has also been associated with increased white matter changes in frontotemporal dementia and risk of cognitive impairment in ALS. Dementia is common both before and after intracerebral hemorrhage (ICH).

Archetypal mutations frequent in public exome: implications for CADASIL.

Objective: To determine the frequency of distinctive EGFr cysteine altering mutations in the 60,706 exomes of the exome aggregation consortium (ExAC) database.

Methods: ExAC was queried for mutations distinctive for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), namely mutations leading to a cysteine amino acid change in one of the 34 EGFr domains of NOTCH3. The genotype-phenotype correlation predicted by the ExAC data was tested in an independent cohort of Dutch CADASIL patients using quantified MRI lesions.

BANK1 and BLK act through phospholipase C gamma 2 in B-cell signaling.

The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling. Little is know about their interactions with other B-cell signaling molecules or their role in the process.

Fine mapping and conditional analysis identify a new mutation in the autoimmunity susceptibility gene BLK that leads to reduced half-life of the BLK protein.

Objectives: To perform fine mapping of the autoimmunity susceptibility gene BLK and identify functional variants involved in systemic lupus erythematosus (SLE).

Methods: Genotyping of 1163 European SLE patients and 1482 controls and imputation were performed covering the BLK gene with 158 single-nucleotide polymorphisms. Logistic regression analysis was done using PLINK and conditional analyses using GENABEL's test score.

Novel mutation in the epithelial sodium channel causing type I pseudohypoaldosteronism in a patient misdiagnosed with cystic fibrosis.

Unlabelled: Cystic fibrosis (CF) is an inherited disorder with a devastating prognosis. Determination of chloride concentration in sweat has been the gold standard test for diagnosing CF for over 50 years and still remains the primary screening test. However, now that the genetic cause is known and can be studied, genetic confirmation is mandatory in every suspected patient.