Skip to main content
Log in

Insulin-like growth factor 2 cannot be linked to a familial form of Beckwith-Wiedemann syndrome

  • Original Paper
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The Beckwith-Wiedemann syndrome (BWS) is characterised by congenital malformations and organomegaly associated with an increased risk for development of childhood neoplasms. Both a sporadic and a familial form have been described in the literature. It has been suggested that duplications or rearrangements of the short arm of chromosome 11 (11p15.5) underlie the aetiology of the disease. This region of chromosome 11 contains the insulin-like growth factor 2 (IGF2) gene, which has been shown to be parentally imprinted in the sporadic form of the BWS with only the active, paternally-derived allele being duplicated. The familial form of BWS, which exhibits a predominantly maternal inheritance, has been suggested to result from a relaxation of IGF2 imprinting. This could render both parental IGF2 alleles active, thereby generating a similar gene dosage as in the sporadic from of the BWS. To address this issue, we used an RNase protection assay based upon a polymorphic region within exon nine of IGF2. We show here that only the paternally-inherited IGF2 allele is transcriptionally active in the index patient of one family with inherited BWS. In addition, highly informative IGF2 DNA markers were used to perform linkage analysis. Since these data ruled out a common maternally-transmitted IGF2 allele in the affected patients, we argue that IGF2 cannot be linked to the hereditary form to the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BWS :

BeckwithWiedemann Syndrome

IGF2 :

insulin-like growth factor 2

References

  1. Aleck KA, Hadro TA (1989) Dominant inheritance of Wiedemann-Beckwith syndrome: further evidence for transmission of “unstable premutation” through carrier women. Am J Med Genet 33:155–160

    Google Scholar 

  2. Beckwith JB (1969) Macroglossia, omphalocele, adrenal cytomegaly, gigantism and hyperplastic visceromegaly. Birth Defects 5:188–196

    Google Scholar 

  3. Brown KW, Williams JC, Maitland NJ, Mott MG (1990) Genomic imprinting and Beckwith-Wiedemann syndrome. Am J Hum Genet 46: 1000–1001

    Google Scholar 

  4. Chomcynski P, Sacchi N (1987) A single-step method for isolation of RNA. Anal Biochem 162:156–159

    Google Scholar 

  5. Fluge G (1975) Neurological findings at follow-up in neonatal hypoglycaemia. Acta Paediatr Scand 64: 629–637

    Google Scholar 

  6. Henry I, Jeanpierre M, Couillin P, Barichard F, Serre JL, Journel H, Lamouroux A, Turleau C, Grouchy J de, Junien C (1989) Molecular definition of the 11p15.5 region involved in Beckwith-Wiedemann syndrome and probably in predisposition to adrenocortical carcinoma. Hum Genet 81: 273–277

    Google Scholar 

  7. Henry I, Bonaiti-Pellié C, Chehensse C, Beldjord C, Schwartz C, Utermann G, Junien C (1991) Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature 351:665–667

    Google Scholar 

  8. Humble RE (1990) Insulin-like growth factors I and II. Eur J Biochem 190:445–462

    Google Scholar 

  9. Irving I (1970) The EMG syndrome. Prog Pediatr Surg 1: 1–61

    Google Scholar 

  10. Jansen M, et al. (1990) Structure and expression of the insulin-like growth factor II (IGF-11) gene. In: Sara V, et al. (eds) Growth factors: from genes to clinical application. Raven Press, New York, 25–40

    Google Scholar 

  11. Journel H, Lucas J, Allaire C, et al. (1985) Trisomy 11p15 and Beckwith-Wiedemann syndrome: report of two new cases. Ann Genet 28:97–101

    Google Scholar 

  12. Julier C, Hyer RN, Davies J, Merlin F, Soularue P, Briant L, Cathelineau G, Deschamps I, Rotter JI, Froguel P, Boitard C, Bell JI, Lathrop BM (1991) Insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature 354:155–159

    Google Scholar 

  13. Junien C (1992) Beckwith-Wiedemann syndrome, tumorigenesis and imprinting. Curr Op Genet Dev 2:431–438

    Google Scholar 

  14. Kosseff AL, Herrman J, Gilbert EF, Viseskul C, Lubinsky M, Opitz JM (1976) Studies of malformation syndromes of man XXIX: the Weidemann-Beckwith syndrome. Clinical, genetic and pathogenetic studies of 12 cases. Eur J Pediatr 123:139–166

    Google Scholar 

  15. Koufos A, Grundy P, Morgan K, Aleck KA, Hadro T, Lampkin BC, Kalbakji A, Cavenee WC (1989) Familial Beckwith-Wiedemann syndrome and a second Wilms' tumour locus both map to 11p15.5. Am J Hum Genet 44: 711–719

    Google Scholar 

  16. Lubinsky M, Herrman J, Kosseff A, Opitz JM (1974) Autosomal-dominant sex-dependent transmission of the Wiedemann-Beckwith syndrome. Lancet I:932

    Google Scholar 

  17. Mouton C, Junien C, Henry I, Bonaiti-Pellié C (1992) Beckwith-Wiedemann syndrome; a demonstration of the mechanism responsible for the excess of transmitting females. J Med Genet 29:217–220

    Google Scholar 

  18. Niikawa N, Ishikaryima S, Takahashi S, Inagawa A, Tonoki H, Ohta Y, Hase N, Kamie T, Kajii T (1986) The Wiedemann — Beckwith syndrome. Pedigree studies on 5 families with evidence for autosomal dominant inheritance with variable expresivity. Am J Med Genet 24:41–55

    Google Scholar 

  19. Ogawa O, Eccles MR, Szeto J, McNoe LA, Yun K, Maw M, Smith PJ, Reeve AE (1993) Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumor. Nature 362: 749–751

    Google Scholar 

  20. Ohlsson R, Holmgren L, Glaser A, Szpecht A, Pfeifer-Ohlsson S (1989) Insulin-like growth-factor 2 and short-range stimulatory loops in control of human placental growth. EMBO J 8: 1993–1999

    Google Scholar 

  21. Ohlsson R, Nyström A, Pfeifer-Ohlsson S, Töhönen V, Hedborg F, Schofield P, Flam F, Ekström TJ (1993) IGF2 is parentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome. Nature Genet 4: 94–97

    Google Scholar 

  22. Pettenati MJ, Haines JL, Higgins RR, Wappner RS, Palmer CG, Weaver DD (1986) Wiedemann-Beckwith syndrome. Presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Hum Genet 74: 143–154

    Google Scholar 

  23. Ping AJ, Reeve AE, Law DJ, Young MR, Boehnke M, Feimberg AP (1989) Genetic linkage of Beckwith-Wiedemann Syndrome to 11p15. Am J Hum Genet 44:720–723

    Google Scholar 

  24. Rainier S, Johnson LA, Dobry CJ, Ping AJ, Grundy PE, Feinberg AP (1993) Relaxation of imprinted genes in human cancer. Nature 362:747–749

    Google Scholar 

  25. Singh M, Singhal PK, Paul VK, Deorari AK, Sundarama KR, Gheropade MD, Agadi A (1991) Neurodevelopmental outcome of asymptomatic and symptomatic babies with neonatal hypoglycaemia. Indian J Med Res 94: 6–10

    Google Scholar 

  26. Turleau C, Grouchy J de, Chavin-Colin F, Martelli H, Voyer M, Charlas R (1984) Trisomy 11p15 and Beckwith-Wiedemann syndrome. A report of two cases. Hum Genet 67:219–221

    Google Scholar 

  27. Wales JKH, Walker W, Moore IE, Clayton PT (1986) Bronze baby syndrome, biliary hypoplasia, incomplete Beckwith-Wiedemann syndrome and partial trisomy 11. Eur J Pediatr 145:141–143

    Google Scholar 

  28. Waziri M, Patil SR, Hanson JW, Bartley JA (1983) Abnormality of chromosome 11 in patients with features of Beckwith-Wiedemann syndrome. J Pediatr 102: 873–876

    Google Scholar 

  29. Wiedemann HR (1964) Complex malformatif familial avec hernie ombilicale et macroglossie. Un syndrome noveau? J Genet Hum 13:223–232

    Google Scholar 

  30. Wiedemann HR (1983) Tumor and hemihypertrophy associated with the Wiedemann-Beckwith syndrome. Eur J Pediatr 141:129

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nyström, A., Hedborg, F. & Ohlsson, R. Insulin-like growth factor 2 cannot be linked to a familial form of Beckwith-Wiedemann syndrome. Eur J Pediatr 153, 574–580 (1994). https://doi.org/10.1007/BF02190661

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02190661

Key words

Navigation