Anti-Growth hormone monoclonal antibody, clone HI-16

Background: Mutations in the genes encoding for GHRH receptor (GHRHR) and GH (GH1) are the most common cause of familial isolated GH deficiency (IGHD). GHRHR mutations are often associated with anterior pituitary hypoplasia (APH), but this has been reported almost exclusively in children older than 8 yr. We analyzed the GHRHR and measured pituitary size in a consanguineous family with the father and three of the five siblings with IGHD. Objective: The aim of the study was to find the mutated gene in a family with severe IGHD. Methods: We sequenced the whole GHRHR coding regions and the intron-exon boundaries from peripheral DNA of the index patient. After identifying the novel mutation, we sequenced the region of interest in the other members of the family. We measured the anterior pituitary volume from magnetic resonance imaging (MRI). Results: The father and the three affected children were homozygous for a new frame-shift mutation in the coding sequence of exon 4 (corresponding to the extracellular domain of the receptor) (c.391delG) that places the downstream sequence out of frame. The mother and two unaffected siblings were heterozygous for the mutation. Two of the affected children had MRI evidence of APH before reaching 6 yr of age. Conclusions: We describe a new mutation in the GHRHR in a family with IGHD. The presence of frank APH before age 6 yr shows that MRI-evident reduced pituitary size can be present in GHRHR mutations even in children younger than 8 yr of age. (J Clin Endocrinol Metab 96: 2982-2986, 2011)

Background: Our study focuses on the role that human Cytomegalovirus (CMV) genotypes play in the development of disease. Objectives: (1) To analyze the frequency of various genotype envelope proteins (gB, gH) in a group of solid organ transplant (SOT) recipients; (2) to assess their correlation with CMV disease; (3) to study the association between any of the genotypes and viral loads. Study design: A retrospective observational study conducted by analyzing CMV gB and gH genotypes detected with real-time polymerase chain reaction (PCR)-specific assays in 162 CMV-positive blood samples from 62 SOT recipients. Demographic, clinical, and microbiological data were recorded. Results: Mixed gB genotypes were associated with viral syndrome (70%, p = .004), earlier presentation of symptoms (48.27 +/- 27.03 versus 74.33 +/- 47.25 days, respectively, p = .001), and higher median of the plasma viral load log(10) (UI/ml) than infection with a single genotype (p = .004). Furthermore, the gB3 genotype was detected more frequently in patients who presented with asymptomatic viremia (77.27%, p < .0001). The gH1 genotype was more frequent (65%) in patients who presented with asymptomatic viremia (p = .003), and it caused infection later than gH2 or the mixed genotype (84.88 +/- 48.10 versus 57.91 +/- 39.18 days, respectively, p < .001). Conclusions: Patients who presented mixed gB genotypes more frequently developed clinical manifestations and earlier, higher, plasma viral loads. The detection of gB and gH genotypes by real-time PCR can provide relevant information to stratify the risk of SOT recipients to develop symptomatic infection by CMV.