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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma


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2191-0251
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Volume 29, Issue 5

Issues

A novel ALMS1 homozygous mutation in two Turkish brothers with Alström syndrome

Caley Laxer
  • Genetics and Genomic Medicine Programme, UCL Institute of Child Health and Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS, London, UK
  • Other articles by this author:
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/ Sofia A. Rahman
  • Genetics and Genomic Medicine Programme, UCL Institute of Child Health and Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS, London, UK
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Maha Sherif
  • Genetics and Genomic Medicine Programme, UCL Institute of Child Health and Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS, London, UK
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/ Sophia Tahir
  • Genetics and Genomic Medicine Programme, UCL Institute of Child Health and Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS, London, UK
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  • De Gruyter OnlineGoogle Scholar
/ Atilla Cayir / Huseyin Demirbilek
  • Genetics and Genomic Medicine Programme, UCL Institute of Child Health and Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS, London, UK
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/ Khalid Hussain
  • Corresponding author
  • Genetics and Genomic Medicine Programme, UCL Institute of Child Health and Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS, London, UK
  • Email
  • Other articles by this author:
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Published Online: 2016-02-24 | DOI: https://doi.org/10.1515/jpem-2015-0249

Abstract

Background: Alström syndrome (AS) is an extremely rare, autosomal recessive disorder characterised by multi-organ features that typically manifest within the first two decades of life. AS is caused by mutations in the Alström syndrome 1 (ALMS1) gene located at 2p13.1.

Methods: In the current study, two brothers from a first-cousin consanguineous family presented with a complex phenotype and were suspected of having AS.

Results: Both brothers were found to be homozygous for a novel nonsense c.7310C>A (p.S2437X) mutation in exon-8 of ALMS1 gene. The consanguineous parents were sequenced and both were heterozygous for the same mutation.

Conclusions: This particular mutation has never been reported before and confirmed the diagnosis of AS in the patients. Our work identifies a novel mutation in ALMS1 gene responsible for the complex phenotype of AS in these patients.

Keywords: Alström syndrome; diabetes mellitus; genetic diagnosis; monogenic obesity

References

  • 1.

    Alstrom CH, Hallgren B, Nilsson LB, Asander H. Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness: a specific syndrome (not hitherto described) distinct from the Laurence-Moon-Bardet-Biedl syndrome: a clinical, endocrinological and genetic examination based on a large pedigree. Acta Psychiatr Neurol Scand Suppl 1959;129:1–35.Google Scholar

  • 2.

    Marshall JD, Bronson RT, Collin GB, Nordstrom AD, Maffei P, et al. New Alstrom syndrome phenotypes based on the evaluation of 182 cases. Arch Intern Med 2005;165:675–83.Google Scholar

  • 3.

    Collin GB, Marshall JD, Ikeda A, So WV, Russell-Eggitt I, et al. Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome. Nat Genet 2002;31:74–8.Google Scholar

  • 4.

    Marshall JD, Maffei P, Collin GB, Naggert JK. Alstrom syndrome: genetics and clinical overview. Curr Genomics 2011;12:225–35.Google Scholar

  • 5.

    Collin GB, Marshall JD, Cardon LR, Nishina PM. Homozygosity mapping at Alstrom syndrome to chromosome 2p. Hum Mol Genet 1997;6:213–9.Google Scholar

  • 6.

    Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, et al. Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res 1997;4:141–50.Google Scholar

  • 7.

    Hearn T, Renforth GL, Spalluto C, Hanley NA, Piper K, et al. Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome. Nat Genet 2002;31:79–83.Google Scholar

  • 8.

    Marshall JD, Hinman EG, Collin GB, Beck S, Cerqueira R, et al. Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alstrom syndrome. Hum Mutat 2007;28:1114–23.Google Scholar

  • 9.

    Pereiro I, Hoskins BE, Marshall JD, Collin GB, Naggert JK, et al. Arrayed primer extension technology simplifies mutation detection in Bardet-Biedl and Alstrom syndrome. Eur J Hum Genet 2011;19:485–8.Web of ScienceGoogle Scholar

  • 10.

    Marshall JD, Muller J, Collin GB, Milan G, Kingsmore SF, et al. Alstrom syndrome: mutation spectrum of ALMS1. Hum Mutat 2015;36:660–8.Google Scholar

  • 11.

    Ozanturk A, Marshall JD, Collin GB, Duzenli S, Marshall RP, et al. The phenotypic and molecular genetic spectrum of Alstrom syndrome in 44 Turkish kindreds and a literature review of Alstrom syndrome in Turkey. J Hum Genet 2015;60:1–9.Web of ScienceGoogle Scholar

  • 12.

    Li G, Vega R, Nelms K, Gekakis N, Goodnow C, et al. A role for Alstrom syndrome protein, alms1, in kidney ciliogenesis and cellular quiescence. PLoS Genet 20075;3:e8.Web of ScienceGoogle Scholar

  • 13.

    Han YG, Spassky N, Romaguera-Ros M, Garcia-Verdugo JM, Aguilar A, et al. Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci 2008;11:277–84.Google Scholar

  • 14.

    Andersen JS, Wilkinson CJ, Mayor T, Mortensen P, Nigg EA, et al. Proteomic characterization of the human centrosome by protein correlation profiling. Nature 2003;426:570–4.Google Scholar

  • 15.

    Collin GB, Cyr E, Bronson R, Marshall JD, Gifford EJ, et al. Alms1-disrupted mice recapitulate human Alstrom syndrome. Hum Molec Genet 2005;14:2323–33.Google Scholar

  • 16.

    Hearn T, Spalluto C, Phillips VJ, Renforth GL, Copin N, et al. Subcellular localization of ALMS1 supports involvement of centrosome and basal body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes. Diabetes 2005;54:1581–7.Google Scholar

  • 17.

    Kousta E, Hadjiathanasiou CG, Tolis G, Papathanasiou A. Pleiotropic genetic syndromes with developmental abnormalities associated with obesity. J Pediatr Endocrinol Metab 2009;22:581–92.Google Scholar

About the article

Corresponding author: Professor Khalid Hussain, Genetics and Genomic Medicine Programme, UCL Institute of Child Health and Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS, 30 Guilford Street, WC1N 1EH, London, UK, E-mail:


Received: 2015-06-19

Accepted: 2015-12-30

Published Online: 2016-02-24

Published in Print: 2016-05-01


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 29, Issue 5, Pages 585–589, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2015-0249.

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