Noncoding copy-number variations are associated with congenital limb malformation.

PurposeCopy-number variants (CNVs) are generally interpreted by linking the effects of gene dosage with phenotypes. The clinical interpretation of noncoding CNVs remains challenging. We investigated the percentage of disease-associated CNVs in patients with congenital limb malformations that affect noncoding cis-regulatory sequences versus genes sensitive to gene dosage effects.

Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer.

Background: Activating mutations in KRAS have been suggested as potential predictive and prognostic biomarkers. However, the prognostic impact of specific point mutations remains less clear. This study assessed the prognostic impact of specific KRAS mutations on survival for patients with colorectal cancer.

First report of somatic mosaicism for mutations in STK11 in four patients with Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant cancer predisposition syndrome characterised by gastrointestinal polyposis and mucocutaneous pigmentation. Mutations in STK11, a serine-threonine protein kinase, have been associated with PJS in up to 100 % of published series. The hypothesis that a further genetic locus for PJS exists is controversial.

The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families.

Objective: To characterise the phenotypes associated with the p.A16V mutation of PRSS1.

Design: Clinical and epidemiological data were collected for any family in which a p.

A reference interval for sweat chloride in infants aged between five and six weeks of age.

Background: This study was designed to establish a reference interval for sweat chloride for infants without evidence of cystic fibrosis (CF), aged between 5 wk and 6 wk, a time when sweat testing is an integral part of newborn screening for CF. In addition, we compared the gold standard method of sweat testing (quantitative pilocarpine iontophoresis [QPIT, coulometry]) with an emerging methodology (Macroduct [ISE]).

Methods: This was a prospective study on healthy infants at 5-6 wk of age.

Cystic fibrosis transmembrane conductance regulator ion channel function testing in recurrent acute pancreatitis.

Goals: To understand the relationship between acute recurrent pancreatitis and cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction.

Background: An emerging number of patients present with a nonclassic phenotype of cystic fibrosis (CF) with partial features or single-organ disease only. The association between the phenotype of recurrent pancreatitis CFTR dysfunction is unclear.

Genetic polymorphisms on the factor V gene in women with recurrent miscarriage and acquired APCR.

Background: Recurrent miscarriage (RM) has been associated with the thrombophilia, activated protein C resistance (APCR). The factor V Leiden mutation located on the B domain of the factor V gene, causes 95% of APCR and since the B domain is pivotal to APCR, it seemed plausible that other mutations or polymorphisms affecting this active domain may instigate acquired APCR. The objective of this study was to determine whether other polymorphisms exist on the parts of the gene encoding the B domain of the factor V in women with acquired APCR and RM.

Nemaline myopathy caused by absence of alpha-skeletal muscle actin.

Objective: To investigate seven congenital myopathy patients from six families: one French Gypsy, one Spanish Gypsy, four British Pakistanis, and one British Indian. Three patients required mechanical ventilation from birth, five died before 22 months, one is ventilator-dependent, but one, at 30 months, is sitting with minimal support. All parents were unaffected.

Monitoring standards for molecular genetic testing in the United Kingdom, the Netherlands, and Ireland.

Molecular genetic techniques have entered many areas of clinical practice. Public expectations from this technology are understandably high. To maintain confidence in this technology, laboratories must implement the highest standards of quality assurance (QA).

Spectrum of factor XI (F11) mutations in the UK population--116 index cases and 140 mutations.

Factor XI deficiency is an autosomal bleeding disorder of variable severity. It is particularly common in the Ashkenazi Jewish population, the result of two founder mutations - E117X and F283L. Recent studies have shown the causative mutations of Factor XI deficiency, outside the Ashkenazi Jewish population, to be highly heterogeneous.

Increased risk of idiopathic chronic pancreatitis in cystic fibrosis carriers.

Cystic fibrosis (CF) is a recessive disease caused by mutations of the CF transmembrane conductance regulator (CFTR) gene. The risk of idiopathic chronic pancreatitis (ICP) is increased in individuals who have CFTR genotypes containing a CF-causing mutation plus a second pathogenic allele. It is unknown whether the risk of ICP is increased in CF carriers who have one CF-causing mutation plus one normal allele.

The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.

LMX1B is a LIM-homeodomain transcription factor required for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons. Heterozygous loss-of-function mutations in LMX1B cause nail patella syndrome (NPS). To further understand LMX1B gene regulation and to identify pathogenic mutations within the coding region, a detailed analysis of LMX1B gene structure was undertaken.

Genetic polymorphisms and retinopathy of prematurity.

Purpose: Retinopathy of prematurity (ROP) is a major problem among very preterm survivors of neonatal intensive care. Neovascularization of the retina is prominent in the proliferative stages of ROP and is under the control of several factors such as vascular endothelial growth factor (VEGF). This study was undertaken on the hypothesis that genetic polymorphisms of VEGF, transforming growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha would occur more frequently in preterm infants with progressive ROP than in those with mild or no disease.