A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism.
Genetic studies in patients with severe early-onset obesity have provided insights into the molecular and physiological pathways that regulate body weight in humans. We report a 19-year-old male with hyperphagia and severe obesity, mild learning difficulties and hypogonadism, in whom diagnostic test...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1797089367998595072 |
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| author | de Smith, A Purmann, C Walters, R Ellis, R Holder, SE Haelst, V Brady, A Fairbrother, U Dattani, M Keogh, J Henning, E Yeo, G O'Rahilly, S Froguel, P Farooqi, I Blakemore, A |
| author_facet | de Smith, A Purmann, C Walters, R Ellis, R Holder, SE Haelst, V Brady, A Fairbrother, U Dattani, M Keogh, J Henning, E Yeo, G O'Rahilly, S Froguel, P Farooqi, I Blakemore, A |
| author_sort | de Smith, A |
| collection | OXFORD |
| description | Genetic studies in patients with severe early-onset obesity have provided insights into the molecular and physiological pathways that regulate body weight in humans. We report a 19-year-old male with hyperphagia and severe obesity, mild learning difficulties and hypogonadism, in whom diagnostic tests for Prader-Willi syndrome (PWS) had been negative. We carried out detailed clinical and metabolic phenotyping of this patient and investigated the genetic basis of this obesity syndrome using Agilent 185 k array comparative genomic hybridization (aCGH) and Affymetrix 6.0 genotyping arrays. The identified deletion was validated using multiplex ligation-dependent probe amplification and long-range PCR, followed by breakpoint sequencing which enabled precise localization of the deletion. We identified a approximately 187 kb microdeletion at chromosome 15q11-13 that encompasses non-coding small nucleolar RNAs (including HBII-85 snoRNAs) which were not expressed in peripheral lymphocytes from the patient. Characterization of the clinical phenotype revealed increased ad libitum food intake, normal basal metabolic rate when adjusted for fat-free mass, partial hypogonadotropic hypogonadism and growth failure. We have identified a novel deletion on chromosome 15q11-13 in an individual with hyperphagia, obesity, hypogonadism and other features associated with PWS, which is normally caused by deficiency of several paternally expressed imprinted transcripts within chromosome 15q11-13, a region that includes multiple protein-coding genes as well as several non-coding snoRNAs. These findings provide direct evidence for the role of a particular family of non-coding RNAs, the HBII-85 snoRNA cluster, in human energy homeostasis, growth and reproduction. |
| first_indexed | 2024-03-07T03:03:08Z |
| format | Journal article |
| id | oxford-uuid:b19e8f2c-1ea8-4dd5-89d2-e2dd584a82e2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:03:08Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:b19e8f2c-1ea8-4dd5-89d2-e2dd584a82e22022-03-27T04:05:30ZA deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b19e8f2c-1ea8-4dd5-89d2-e2dd584a82e2EnglishSymplectic Elements at Oxford2009de Smith, APurmann, CWalters, REllis, RHolder, SEHaelst, VBrady, AFairbrother, UDattani, MKeogh, JHenning, EYeo, GO'Rahilly, SFroguel, PFarooqi, IBlakemore, AGenetic studies in patients with severe early-onset obesity have provided insights into the molecular and physiological pathways that regulate body weight in humans. We report a 19-year-old male with hyperphagia and severe obesity, mild learning difficulties and hypogonadism, in whom diagnostic tests for Prader-Willi syndrome (PWS) had been negative. We carried out detailed clinical and metabolic phenotyping of this patient and investigated the genetic basis of this obesity syndrome using Agilent 185 k array comparative genomic hybridization (aCGH) and Affymetrix 6.0 genotyping arrays. The identified deletion was validated using multiplex ligation-dependent probe amplification and long-range PCR, followed by breakpoint sequencing which enabled precise localization of the deletion. We identified a approximately 187 kb microdeletion at chromosome 15q11-13 that encompasses non-coding small nucleolar RNAs (including HBII-85 snoRNAs) which were not expressed in peripheral lymphocytes from the patient. Characterization of the clinical phenotype revealed increased ad libitum food intake, normal basal metabolic rate when adjusted for fat-free mass, partial hypogonadotropic hypogonadism and growth failure. We have identified a novel deletion on chromosome 15q11-13 in an individual with hyperphagia, obesity, hypogonadism and other features associated with PWS, which is normally caused by deficiency of several paternally expressed imprinted transcripts within chromosome 15q11-13, a region that includes multiple protein-coding genes as well as several non-coding snoRNAs. These findings provide direct evidence for the role of a particular family of non-coding RNAs, the HBII-85 snoRNA cluster, in human energy homeostasis, growth and reproduction. |
| spellingShingle | de Smith, A Purmann, C Walters, R Ellis, R Holder, SE Haelst, V Brady, A Fairbrother, U Dattani, M Keogh, J Henning, E Yeo, G O'Rahilly, S Froguel, P Farooqi, I Blakemore, A A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism. |
| title | A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism. |
| title_full | A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism. |
| title_fullStr | A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism. |
| title_full_unstemmed | A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism. |
| title_short | A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism. |
| title_sort | deletion of the hbii 85 class of small nucleolar rnas snornas is associated with hyperphagia obesity and hypogonadism |
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