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Michael Ogrady - One of the best experts on this subject based on the ideXlab platform.
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po 0069 terminal deletion of Chromosome 15q resulting in haploinsufficiency of the igf 1 receptor and marked elevation of igf 1
Archives of Disease in Childhood, 2014Co-Authors: A Oriordan, N Mcgrath, Farhana Sharif, Michael OgradyAbstract:Introduction Ten to fifteen percent of small for gestational age (SGA) infants demonstrate failure of catch-up growth. Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene due to monosomy 15q is an extremely rare cause with 16 cases reported in the literature. We describe the phenotype of such a patient including biochemical findings, auxology and management. Case A three-year-old female with global developmental delay and autistic spectrum disorder was evaluated for short stature. Height was 82 cm (-3.7 SDS) and weight was 12.5 kg (-1.3 SDS). She was born at term weighing 2.88 kg and was microcephalic and dysmorphic. Array CGH revealed an unbalanced translocation resulting in trisomy of the terminal portion of Chromosome 10p and monosomy 15q26.3- >qter which contains the region coding for IGF1R. IGF-1(243 µg/L) and IGFBP-3 (3501 ng/ml) levels were markedly elevated; +4.7 SDS and +3.3 SDS respectively. The marked elevation in IGF-1 levels was considered a relative contraindication to GH therapy. Discussion Haploinsufficency of IGF1R gene is associated with elevated levels of IGF-1 as a result of target organ resistance. Exogenous growth hormone, while further elevating IGF-1, in many cases facilitates catch-up growth albeit to a lesser extent than other ex-SGA infants. In this case IGF-1 levels were exceptionally high, precluding growth hormone therapy. Conclusion Deletions involving the IGF1R gene are a rare but treatable cause of short stature. This case is unusual however, as marked elevation of IGF-1 at baseline precluded GH therapy.
A Oriordan - One of the best experts on this subject based on the ideXlab platform.
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po 0069 terminal deletion of Chromosome 15q resulting in haploinsufficiency of the igf 1 receptor and marked elevation of igf 1
Archives of Disease in Childhood, 2014Co-Authors: A Oriordan, N Mcgrath, Farhana Sharif, Michael OgradyAbstract:Introduction Ten to fifteen percent of small for gestational age (SGA) infants demonstrate failure of catch-up growth. Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene due to monosomy 15q is an extremely rare cause with 16 cases reported in the literature. We describe the phenotype of such a patient including biochemical findings, auxology and management. Case A three-year-old female with global developmental delay and autistic spectrum disorder was evaluated for short stature. Height was 82 cm (-3.7 SDS) and weight was 12.5 kg (-1.3 SDS). She was born at term weighing 2.88 kg and was microcephalic and dysmorphic. Array CGH revealed an unbalanced translocation resulting in trisomy of the terminal portion of Chromosome 10p and monosomy 15q26.3- >qter which contains the region coding for IGF1R. IGF-1(243 µg/L) and IGFBP-3 (3501 ng/ml) levels were markedly elevated; +4.7 SDS and +3.3 SDS respectively. The marked elevation in IGF-1 levels was considered a relative contraindication to GH therapy. Discussion Haploinsufficency of IGF1R gene is associated with elevated levels of IGF-1 as a result of target organ resistance. Exogenous growth hormone, while further elevating IGF-1, in many cases facilitates catch-up growth albeit to a lesser extent than other ex-SGA infants. In this case IGF-1 levels were exceptionally high, precluding growth hormone therapy. Conclusion Deletions involving the IGF1R gene are a rare but treatable cause of short stature. This case is unusual however, as marked elevation of IGF-1 at baseline precluded GH therapy.
Michael Strober - One of the best experts on this subject based on the ideXlab platform.
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significant linkage on Chromosome 10p in families with bulimia nervosa
American Journal of Human Genetics, 2003Co-Authors: Cynthia M Bulik, Bernie Devlin, Silviu Alin Bacanu, Laura Thornton, Kelly L Klump, Manfred M Fichter, Katherine A Halmi, Allan S Kaplan, Michael StroberAbstract:Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susceptibility to BN, we conducted a linkage analysis of multiplex families with eating disorders that were identified through a proband with BN. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multipoint maximum LOD score (MLS), of 2.92, on Chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it can be measured, we performed linkage analysis in a subset (n=133) of families in which at least two affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on Chromosome 10, between markers D10S1430 and D10S1423. These results provide evidence of the presence of a susceptibility locus for BN on Chromosome 10p. Using simulations, we demonstrate that both of these scores, 2.92 and 3.39, meet the widely accepted criterion for genomewide significance. Another region on 14q meets the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 centimorgans from p-ter.
Steven Wiltshire - One of the best experts on this subject based on the ideXlab platform.
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Significant linkage of BMI to Chromosome 10p in the U.K. population and evaluation of GAD2 as a positional candidate.
Diabetes, 2006Co-Authors: Christopher J. Groves, Eleftheria Zeggini, Mark Walker, Graham A. Hitman, Jonathan C. Levy, Stephen O'rahilly, Andrew T. Hattersley, Mark I. Mccarthy, Steven WiltshireAbstract:Obesity is a major health problem, and many family-based studies have suggested that it has a strong genetic basis. We performed a genome-wide quantitative trait linkage scan for loci influencing BMI in 573 pedigrees from the U.K. We identified genome-wide significant linkage (logarithm of odds = 3.74, between D10S208 and D10S196, genome-wide P = 0.0186) on Chromosome 10p. The size of our study population and the statistical significance of our findings provide substantial contributions to the body of evidence for a locus on Chromosome 10p. We examined eight single nucleotide polymorphisms (SNPs) in GAD2, which maps to this linkage region, tagging the majority of variation in the gene, and observed marginally significant (0.01
Allan S Kaplan - One of the best experts on this subject based on the ideXlab platform.
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significant linkage on Chromosome 10p in families with bulimia nervosa
American Journal of Human Genetics, 2003Co-Authors: Cynthia M Bulik, Bernie Devlin, Silviu Alin Bacanu, Laura Thornton, Kelly L Klump, Manfred M Fichter, Katherine A Halmi, Allan S Kaplan, Michael StroberAbstract:Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susceptibility to BN, we conducted a linkage analysis of multiplex families with eating disorders that were identified through a proband with BN. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multipoint maximum LOD score (MLS), of 2.92, on Chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it can be measured, we performed linkage analysis in a subset (n=133) of families in which at least two affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on Chromosome 10, between markers D10S1430 and D10S1423. These results provide evidence of the presence of a susceptibility locus for BN on Chromosome 10p. Using simulations, we demonstrate that both of these scores, 2.92 and 3.39, meet the widely accepted criterion for genomewide significance. Another region on 14q meets the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 centimorgans from p-ter.