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Localization of the gene for familial partial lipodystrophy (Dunnigan variety) to chromosome 1q21–22

Nature Genetics volume 18, pages 292–295 (1998)Cite this article

Abstract

Obesity is strongly implicated in the pathophysiology of insulin resistance, diabetes mellitus and dyslipidemia1–3. The mechanisms, however, by which obesity causes these complications are not known. The study of single-gene disorders affecting adipose tissue may elucidate some of the mechanisms involved in these processes. Familial partial lipodystrophy, Dunnigan variety, (FPLD, OMIM 308980) is an autosomal-dominant condition characterized by marked loss of subcutaneous adipose tissue affecting the trunk and extremities but with excess fat deposition in the head and neck areas4–14. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus, dyslipidemia and acanthosis nigricans4–14. The genetic basis of FPLD is unknown. We carried out a genome-wide scan with a set of highly polymorphic short tandem-repeats (STR) in individuals from five well-characterized pedigrees and mapped the FPLD locus to chromosome 1q21–22. The maximum two-point lod score obtained with a highly polymorphic microsatellite at D1S2624 at θmax=0 was 5.84. Multipoint-linkage analysis yielded a peak lod score of 8.25 between D75305 and D1S1600. There was no evidence for genetic heterogeneity (α=1) in the pedigrees.

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References

  1. Reaven, G.M. Role of insulin resistance in human disease. Diabetes 37, 1595–1607 (1988).

    Article  CAS  PubMed  Google Scholar 

  2. DeFronzo, R.A. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerosis. Neth. J. Med. 50, 191–197 (1997).

    Article  CAS  PubMed  Google Scholar 

  3. Landsberg, L. Obesity and the insulin resistance syndrome. Hypertens. Res. 19, S51–55 (1996).

    Article  PubMed  Google Scholar 

  4. Ozer, F.L., Lichtenstein, J.R., Kwiterovich, P.O. & McKusick, V.A. A new genetic variety of lipodystrophy. Clin. Res. 21, 533 (1973)

  5. Dunnigan, M.G., Cochrane, M.A., Kelly, A. & Scott, J.W. Familial lipoatrophic diabetes with dominant transmission: a new syndrome. Q. J. Med. 49, 33–48 (1974).

    Google Scholar 

  6. Kobberling, J., Willms, B., Kattermann, R. & Creutzfeldt, W. Lipodystrophy of the extremities. A dominantly inherited syndrome associated with lipoatrophic diabetes. Humangenetik 29, 111–120 (1975).

    CAS  PubMed  Google Scholar 

  7. Kobberling, J. & Dunnigan, M.G. Familial partial lipodystrophy: two types of an X linked dominant syndrome, lethal in the hemizygous state. J. Med. Genet 23, 120–127 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Davidson, M.B. & Young, R.T. Metabolic studies in familial partial lipodystrophy of the lower trunk and extremities. Diabetologia 11, 561–568 (1975).

    Article  CAS  PubMed  Google Scholar 

  9. Kobberling, J. et al. Partielle Lipodystrophie mit lipatrophischem Diabetes und Hyperlipoproteinamie. Verh. Dtsch. Ges. Inn. Med. 87, 958–961 (1981).

    Google Scholar 

  10. Burn, J. & Baraitser, M. Partial lipoatrophy with insulin resistant diabetes and hyperlipidaemia (Dunnigan syndrome). J. Med. Genet. 23, 128–130 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Robbins, D.C., Norton, E.S., Tulp, O. & Sims, E.A.H. Familial partial lipodystrophy: complications of obesity in the non-obese? Metabolism 31, 445–452 (1982).

    Article  CAS  PubMed  Google Scholar 

  12. Lillystone, D. & West, R.J. Lipodystrophy of limbs associated with insulin resistance. Arch. Dis. Child. 50, 737–739 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hook, B., Freudlsperger, F., Adam, W. & Seif, F.J. Partielles lipodystrophie-syndrom (Typ Dunnigan). Hautarzt 35, 530–535 (1984).

    CAS  PubMed  Google Scholar 

  14. Jackson, S.N., Howlett, T.A., McNally, P.G., O'Rahilly, S. & Trembath, R.C. Dunnigan-Kobberling syndrome: an autosomal dominant form of partial lipodystrophy. Q. J. Med. 90, 27–36 (1997).

    Article  CAS  Google Scholar 

  15. Flagiello, D. et al. Assignment of the genes for cellular retinoic acid binding protein 1 (CRABP1) and 2 (CRABP2) to human chromosome band 15q24 and 1q21.3, respectively, by in situ hybridization. Cytogenet. Cell. Genet. 76, 17–18 (1997).

    Article  CAS  PubMed  Google Scholar 

  16. Johnson, B. et al. The Ah receptor nuclear translocator (ARNT) is located on q21 of human chromosome 1 and on mouse chromosome 3 near Cf-3. Genomics 17, 592–598(1993).

    Article  CAS  PubMed  Google Scholar 

  17. Wanner, R., Panteleyev, A., Henz, B.M. & Rosenbach, T. Retinoic acid affects the expression rate of the differentiation-related genes aryl hydrocarbon receptor, ARNT and keratin 4 in proliferative keratinocytes only. Biochim. Biophys. Acta. 1317, 105–111(1996).

    Article  CAS  PubMed  Google Scholar 

  18. Marenholz, I. et al. Genetic analysis of the epidermal differentiation complex (EDC) on human chromosome 1q21: chromosomal orientation, new markers, and a 6-Mb YAC contig. Genomics 37, 295–302 (1996).

    Article  CAS  PubMed  Google Scholar 

  19. Feder, J. et al. A systematic approach for detecting high-frequency restriction fragment polymorphisms using large genomic probes. Am. J. Hum. Genet. 37, 635–649 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Kruglyak, L., Daly, M.J., Reeve-Daly, M.P. & Lander, E.S. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am. J. Hum. Genet. 58, 1347–1363 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Lander, E.S. & Green, P. Construction of multilocus genetic linkage maps in humans. Proc. Natl. Acad. Sci. USA 84, 2363–2367 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. Natl. Acad. Sci. USA 81, 3443–3446 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schaffer, A.A., Gupta, S.K., Shriram, K. & Cottingham, R.W., Jr. Avoiding recomputation in linkage analysis. Hum. Hered. 44, 225–237 (1994).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 75235, USA

    John M. Peters, Robert Barnes, Lynda Bennett & Anne M. Bowcock

  2. Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 75235, USA

    William M. Gitomer & Abhimanyu Garg

  3. Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 75235, USA

    Abhimanyu Garg

  4. Center for Mineral Metabolism, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 75235, USA

    William M. Gitomer

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  1. John M. Peters
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Correspondence to Abhimanyu Garg.

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Peters, J., Barnes, R., Bennett, L. et al. Localization of the gene for familial partial lipodystrophy (Dunnigan variety) to chromosome 1q21–22. Nat Genet 18, 292–295 (1998). https://doi.org/10.1038/ng0398-292

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