Survival of Pseudomonas aeruginosa in cystic fibrosis (CF) chronic infections is based on a genetic adaptation process consisting of mutations in specific genes, which can produce advantageous phenotypic switches and ensure its persistence in the lung. Among these, mutations inactivating the regulators MucA (alginate biosynthesis), LasR (quorum sensing) and MexZ (multidrug-efflux pump MexXY) ar...

Multiple endocrine neoplasia type 1 (MEN1; OMIM 131100) is an autosomal-dominant hereditary endocrine tumor syndrome. It is characterized by the combined development of anterior pituitary adenomas, adenomas or hyperplasia of the parathyroid glands, and gastroenteropancreatic neuroendocrine tumors (GEPNETs) in a single patient. Germline mutations in the menin gene (MEN1) account for the developm...

An unexpected revelation of cancer genome studies has been frequent abnormality in genes for factors that modify chromatin, underscored in this issue of Blood by reports from Score et al and Kroeze et al of inactivating mutations and chromosome loss in SUZ12, EED and JARID2 in myelodysplastic syndrome (MDS) and myeloproliferative disease (MPD).

INTRODUCTION Mutations in GJB2 are the most common cause of non-syndromic autosomal recessive hearing impairment, ranging from mild to profound. Mutation analysis of this gene is widely available as a genetic diagnostic test. OBJECTIVE To assess a possible genotype-phenotype correlation for GJB2. DESIGN Retrospective analysis of audiometric data from people with hearing impairment, segregat...

Inactivating germline mutations in DNA mismatch repair (MMR) genes are diagnostic for Lynch syndrome. However, the clinical significance of missense variants is uncertain. A threshold level of compromised MLH1 expression, correlating with greater protein instability and MMR functional defect, has been identified to help classify the pathogenicity of missense variants.

To determine whether AlgL's lyase activity is required for alginate production in Pseudomonas aeruginosa, an algLdelta::Gm(r) mutant (FRD-MA7) was created. algL complementation of FRD-MA7 restored alginate production, but algL constructs containing mutations inactivating lyase activity did not, demonstrating that the enzymatic activity of AlgL is required for alginate production.

Inactivating mutations in the Methyl-CpG Binding Protein 2 (MECP2) gene are main cause of Rett syndrome (RTT). Despite extensive research into MECP2 function, no treatments for RTT currently available. Here, we used an evolutionary genomics approach to construct unbiased network, using 1028 eukaryotic genomes prioritize proteins with strong co-evolutionary signatures MECP2. Focusing on targeted...