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Vol. 62, Suppl. 3, 2004
Issue release date: October 2004
Section title: Advances in Dysmorphology
Horm Res 2004;62(suppl 3):60–65
(DOI:10.1159/000080501)

Molecular Basis of Sotos Syndrome

Niikawa N.
aDepartment of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki; bCREST, Japan Science and Technology Agency, Kawaguchi, Japan

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Article / Publication Details

First-Page Preview
Abstract of Advances in Dysmorphology

Published online: 11/17/2004

Number of Print Pages: 6
Number of Figures: 5
Number of Tables: 2

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: http://www.karger.com/HRP

Abstract

This paper describes the isolation of a novel human gene, NSD1, from the 5q35 breakpoint of t(5;8)(q35; q24.1) in a patient with Sotos syndrome, and NSD1 mutation analysis. Of 112 (95 Japanese and 17 non-Japanese) patients analyzed, 16 (14%) had a heterozygous NSD1 point mutation (10 protein truncation types and six missense types) and 50 (45%) a ∼0.7-Mb microdeletion involving NSD1. The results indicated that haploinsufficiency of NSD1 is the major cause of Sotos syndrome, and NSD1 plays a role in growth and brain development in humans. Detailed clinical examinations provided a genotype-phenotype correlation in Sotos syndrome, i.e. in patients with deletions, overgrowth is less obvious and mental retardation is more severe than in those with point mutations, and major anomalies were exclusively seen in the former. The results also indicated that Sotos syndrome due to a deletion falls into a contiguous gene syndrome, while Sotos syndrome due to an NSD1 point mutation is a single gene defect, occasionally with an autosomal dominant mode of inheritance. The genomic structure around the deleted and flanking regions revealed the presence of two sets of low copy repeats through which the microdeletion in Sotos syndrome is mediated.


Article / Publication Details

First-Page Preview
Abstract of Advances in Dysmorphology

Published online: 11/17/2004

Number of Print Pages: 6
Number of Figures: 5
Number of Tables: 2

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: http://www.karger.com/HRP


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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References

  1. Visser R, Matsumoto N: The genetics of Sotos syndrome. Curr Opin Pediatr 2003;15:598–606.
  2. Sotos JF, Dodge PR, Muirhead D, Crawford JD, Talbot NB: Cerebral gigantism in childhood. N Engl J Med 1964;271:109–116.
  3. Höglund P, Kurotaki N, Kytölä S, Miyake N, Somer M, Matsumoto M: Familial Sotos syndrome is caused by a novel 1 base pair deletion of the NSD1 gene. J Med Genet 2003;40:51–54.
  4. Imaizumi K, Kimura J, Matsuo M, Kurosawa K, Masuno M, Niikawa N, Kuroki Y: Sotos syndrome associated with a de novo balanced reciprocal translocation t(5;8)(q35;q24.1). Am J Med Genet 2002;107:58–60.
  5. Zhu G, Gillessen-Kaesbach G, Wirth J, Passarge E, Bartsch O: Girl with phenotypic abnormalities and a de novo, apparently balanced translocation 46,XX,t(5;10)(q35.2q11.2). Am J Med Genet 2001;98:317–319.
  6. Kurotaki N, Harada N, Yoshiura K, Sugano S, Niikawa N, Matsumoto N: Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene. Gene 2001;279:197–204.
  7. Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T, Ohashi H, Naritomi K, Tsukahara M, Makita Y, Sugimoto T, Sonoda T, Hasegawa T, Chinen Y, Tomita H-A, Kinoshita A, Mizuguchi T, Yoshiura K, Ohta T, Kishino T, Fukushima Y, Niikawa N, Matsumoto N: Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet 2002;30:365–366.
  8. Kurotaki N, Harada N, Shimokawa O, Miyake N, Kawame H, Uetake K, Makita Y, Kondoh T, Ogata T, Hasegawa T, Nagai T, Ozaki T, Touyama M, Shenhav R, Ohashi H, Medne L, Shiihara T, Ohtsu S, Kato Z, Okamoto N, Nishimoto J, Lev D, Miyoshi Y, Ishikiriyama S, Sonoda T, Sakazume S, Fukushima Y, Kurosawa K, Cheng J-F, Yoshiura K, Ohta T, Kishino T, Niikawa N, Matsumoto N: Fifty microdeletions among 112 cases of Sotos syndrome: Low copy repeats possibly mediate the common deletion. Hum Mut 2003;22:378–387.
  9. Suzuki Y, Ishihara D, Sasaki M, Nakagawa H, Hata H, Tsunoda T, Watanabe M, Komatsu T, Ota T, Isogai T, Suyama A, Sugano S: Statistical analysis of the 5′ untranslated region of human mRNA using ‘oligo-capped’ cDNA libraries. Genomics 2000;64:286–297.
  10. Kamimura J, Endo Y, Kurotaki N, Kinoshita A, Miyake N, Shimokawa O, Harada N, Visser R, Ohashi H, Miyakawa K, Gerritsen J, Innes AM, Lagace L, Frydman M, Okamoto N, Puttinger R, Raskin S, Resic B, Culic V, Yoshiura K, Ohta T, Kishino T, Ishikawa M, Niikawa N, Matsumoto N: Identification of eight novel NSD1 mutations in Sotos syndrome. J Med Genet 2003;40:e126.
  11. Miyake N, Sugawara H, Kurotaki N, Shimokawa O, Harada N, Kondoh T, Tsukahara M, Ishikiriyama S, Sonoda T, Miyoshi Y, Sakatsume S, Fukushima Y, Ohashi H, Nagai T, Kawame H, Kurosawa K, Touyama M, Shiihara T, Okamoto N, Nishimoto J, Yoshiura K, Ohta T, Kishino T, Niikawa N, Matsumoto N: Preferential paternal origin of microdeletion as prezygotic chromosome and/or chromatid rearrangements in Sotos syndrome. Am J Hum Genet 2003;72:1331–1337.
  12. Douglas J, Hanks S, Temple IK, Davies S, Murray A, Upadhyaya M, Tomkins S, Hughes HE, Cole TR, Rahman N: NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes. Am J Hum Genet 2003;72:132–143.
  13. Rio M, Clech L, Amiel J, Faivre L, Lyonnet S, Le Merrer M, Odent S, Lacombe D, Edery P, Brauner R, Raoul O, Gosset P, Prieur M, Vekemans M, Munnich A, Colleaux L, Cormier-Daire V: Spectrum of NSD1 mutations in Sotos and Weaver syndromes. J Med Genet 2003;40:436–440.
  14. Stankiewicz P, Lupski JR: Genome architecture, rearrangements and genomic disorders. Trends Genet 2002;18:74–82.
  15. Nagai T, Matsumoto N, Kurotaki N, Harada N, Niikawa N, Ogata T, Imaizumi K, Kurosawa K, Kondoh T, Ohashi H, Tsukahara M, Makita Y, Sugimoto T, Sonoda T, Yokoyama T, Uetake K, Sakazume S, Fukushima Y, Naritomi K: Sotos syndrome and haploinsufficiency of NSD1: Clinical features of intragenic mutations and submicroscopic deletions. J Med Genet 2003;40:285–289.
  16. Kaneko H, Tsukahara M, Tachibana H, Kurashige H, Kuwano A, Kajii T: Congenital heart defects in Sotos sequence. Am J Med Genet 1987;26:569–576.
  17. Cole TR, Hughes HE: Sotos syndrome: a study of the diagnostic criteria and natural history. J Med Genet 1994;31:20–32.
  18. Jaju RJ, Fidler C, Haas OA, Strickson AJ, Watkins F, Clark K, Cross NC, Cheng JF, Aplan PD, Kearney L, Boultwood J, Wainscoat JS: A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. Blood 2001;98:1264–1267.
  19. Cohen MM Jr: Tumors and nontumors in Sotos syndrome. Am J Med Genet 1999;84:173–175.