A polymorphism in the growth hormone receptor is associated with height in children with Prader-Willi syndrome

The exon‐3 deletion polymorphism (d3, Database of Genomic Variants ID: Variation_64191) in the growth hormone receptor (GHR) gene is associated with increased growth response to growth hormone (GH) therapy in GH‐deficient patients. However, an association of the GHR genotype with height has not yet been reported in Prader–Willi syndrome (PWS). The aim of this study was to assess the association of GHR alleles with height before starting GH therapy in patients with PWS. Seventy‐four patients with PWS were genotyped and their medical records were retrospectively reviewed (45 males and 29 females, median age 8.7 years). One hundred normal controls, with known final height, were also genotyped. The GH‐exon 3 locus was genotyped using a PCR multiplex assay. The distribution of alleles in the patients with PWS was not different from controls [(fl/fl n = 53 (72%), fl/d3 n = 21 (28%)) in PWS vs. (fl/fl n = 72(72%), fl/d3 n = 26(26%), and d3/d3 n = 2(2%)]. However, patients with PWS carrying a d3 allele had significantly greater height standard deviation scores (SDS) (P = 0.025) and higher insulin‐like growth factor I (IGF‐I) level (P = 0.041), although the age at the start of GH therapy, weight, BMI, and body fat were not different. The d3 allele was associated with height and IGF‐I levels before GH therapy and suggests that even before GH therapy, d3 allele may influence height through GH secretion. © 2011 Wiley Periodicals, Inc.     

The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean Hereditary Breast Cancer study

The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study and treated at 36 institutions between May 2007 and May 2010. Patients with familial BC were defined as BC patients with family histories of BC or ovarian cancer (OC) in any relatives. All probands received genetic counseling and BRCA genetic testing was performed after obtaining informed consent. The mean age of BC diagnosis was 43.6 years. The numbers of probands with family histories of BC only and OC only were 682 and 93, respectively. The overall prevalence of the BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4 %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA testing. However, the prevalence of the BRCA mutations among subgroups that had 2 BC patients in a family with both age at diagnosis of more than 50 years old did not reach the 10 % criteria (4.1 %). Korean familial BC patients are good candidates for BRCA testing even when they have family histories of single breast cancers. However, proband age at diagnosis should be carefully considered when selecting patients for testing.     

Two novel PEX1 mutations in a patient with Zellweger syndrome: the first Korean case confirmed by biochemical, and molecular evidence

Peroxisome biogenesis disorders (PBD) represent a spectrum of genetic disorders characterized by impaired peroxisome assembly. Zellweger syndrome (ZS) is the most severe form of PBD and is characterized by craniofacial abnormalities, severe hypotonia, neonatal seizures, ocular abnormalities, psychomotor retardation, hepatomegaly and increased levels of very long chain fatty acids (VLCFA). The most common mutation associated with the PBD is PEX1. Here, the first Korean patient with ZS confirmed by clinical, biochemical, and molecular findings is reported. Two novel mutations of the PEX1 gene were identified in the patient with ZS. The patient was a compound heterozygote for c.2034_2035delCA and c.2845C>T mutations of the PEX1 gene. Both mutations are novel findings and were inherited from the patient's parents. In summary, here the first Korean case of ZS is reported that was confirmed by two novel mutations of the PEX1 gene.     

Proteomic analysis of pancreatic juice for the identification of biomarkers of pancreatic cancer

Introduction  

Protein profiles of endoscopically collected pancreatic juice from normal, chronic pancreatitis patients and pancreatic cancer patients were compared to identify diagnostic biomarkers of pancreatic cancer.     

Proinflammatory activity and the sensitization of depressive-like behavior during maternal separation

When guinea pig pups are isolated for a few hours in a novel environment, they exhibit a distinctive passive behavioral response that appears to be mediated by proinflammatory activity. Recently, we observed that pups separated on two consecutive days show an enhanced (sensitized) passive response on the second day. In Experiment 1, pups receiving intracerebroventricular infusion of 50 ng of the anti-inflammatory cytokine interleukin-10 prior to a first separation failed to show a sensitized behavioral response to separation the next day. In Experiment 2, pups separated on Days 1 and 2, or just 2, showed an increase in passive responding during separation on Day 5. Pups injected with the bacterial antigen lipopolysacchride (LPS; 75 μg/kg body weight, intraperitoneal) prior to separation on Day 1 showed an increase in passive behavior several days later not shown by pups injected with saline prior to Day 1 separation. However, injection of LPS without separation on the first day did not enhance responding during an initial separation on the second day. These results suggest that immune activation is necessary, but not sufficient, to account for the sensitization of passive behavior of isolated guinea pig pups the following day, that boosting proinflammatory activity during an initial separation may promote sensitization several days later, and that the sensitized response persists for at least several days.     

Lipid profiles for intrahepatic cholangiocarcinoma identified using matrix-assisted laser desorption/ionization mass spectrometry

BackgroundWe evaluated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis of lipids may distinguish intrahepatic cholangiocarcinomas from adjacent normal tissue and from other adenocarcinomas that frequently metastasize to liver.MethodsFour pairs of frozen surgical specimens of cholangiocarcinomas and adjacent normal tissue were analyzed using histology-directed, MALDI MS analysis. 2,5-dihydroxybenzoic acid / α-cyano-4-hydroxycinnamic acid were manually deposited on tumor-rich areas, and mass spectra were acquired using a MALDI-time of flight instrument.ResultsCholangiocarcinomas and adjacent normal tissue samples demonstrated different lipid profiles, as evidenced by permutation P value < 0.05 for the cross-validated misclassification rate. Cancer-associated lipid alteration was similar between cholangiocarcinomas and pancreatic cancers, but not between cholangiocarcinomas and colorectal cancers. Baseline lipid profiles were different between cholangiocarcinoma and colorectal cancers.ConclusionsMALDI MS analysis of lipid distinguishes cancerous epithelium of cholangiocarcinoma from adjacent normal tissue, and between cholangiocarcinomas and colorectal cancers.