Somatic genetic alterations in tumors are known to correlate with survival, but little is known about the prognostic significance of germ-line variation. We assessed the effect of germ-line variation on survival among women with breast cancer participating in a British population-based study. Up to 2430 cases for whom current vital status data were available were screened for BRCA1/2 mutations ...

Erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism in which decreased activity of ferrochelatase (FECH) leads to accumulation of protoporphyrin IX (PP IX) in red blood cells, plasma, liver, and bile, and increased PP IX excretion in feces. Clinically, EPP is characterized by photosensitivity that begins in early childhood and includes burning, swelling, itching...

BACKGROUND UCP3 is a mitochondrial membrane transporter that is postulated to uncouple oxidative phosphorylation from ATP synthesis producing heat instead of ATP. Human UCP3 is mainly expressed in skeletal muscle, which plays an important role in energy homeostasis and substrate oxidation. Therefore, UCP3 is a good candidate gene for obesity. MATERIALS AND METHODS We analyzed, among 734 subje...

BACKGROUND The GDNF family receptor alpha (GFRalpha) proteins are extracellular cell surface bound molecules that act as adapters in binding of the GDNF family of soluble neurotrophic factors to the RET receptor. These molecules are essential for development of many neural crest derived cell types and the kidney. Mutations in RET and in two members of the GDNF ligand family are associated with ...

The calcium channel alpha(1A) subunit gene codes for proteins with diverse structure and function. This diversity may be important for fine tuning neurotransmitter release at central and peripheral synapses. The alpha(1A) C terminus, which serves a critical role in processing information from intracellular signaling molecules, is capable of undergoing extensive alternative splicing. The purpose...

Mutation spectrum of phenylalanine hydroxylase (PAH) gene in patients with phenylketonuria (PKU) in Northern China is described with a discussion on genotype-phenotype correlation. By using PCR/SSCP and DNA sequencing, all exons of PAH gene in the 185 unrelated patients with PKU from Northern China were studied. A total of 70 different mutations, including 42 missense, 12 splice, 7 nonsense, 5 ...

OBJECTIVE To study the mutations in the ferrochelatase gene (FECH) and the phenotypic expression of erythropoietic protoporphyria (EPP) in a group of Spanish patients. DESIGN Case series. SETTING University-based hospital. PATIENTS Eleven unrelated patients with EPP and 19 asymptomatic relatives from 10 families. MAIN OUTCOMES MEASURES Measurement of protoporphyrin concentration in red ...

CONTEXT Many inherited disorders of calcium and phosphate homeostasis are unexplained at the molecular level. OBJECTIVE The objective of the study was to identify the molecular basis of phosphate and calcium abnormalities in two unrelated, consanguineous families. PATIENTS The affected members in family 1 presented with rickets due to profound urinary phosphate-wasting and hypophosphatemic ...