Array-based Comparative Genomic Hybridization Identifies a High Frequency of Copy Number Variations in Patients with Syndromic Overgrowth

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2009 Oct 22

PMID 19844265

Citations 7

Authors

Valerie Malan

Suzanne Chevallier

Gwendoline Soler

Christine Coubes

Didier Lacombe

Laurent Pasquier

Jean Soulier

Nicole Morichon-Delvallez

Catherine Turleau

Arnold Munnich

Serge Romana

Michel Vekemans

Valerie Cormier-Daire

Laurence Colleaux

Affiliations

Soon will be listed here.

Abstract

Overgrowth syndromes are a heterogeneous group of conditions including endocrine hormone disorders, several genetic syndromes and other disorders with unknown etiopathogenesis. Among genetic causes, chromosomal deletions and duplications such as dup(4)(p16.3), dup(15)(q26qter), del(9)(q22.32q22.33), del(22)(q13) and del(5)(q35) have been identified in patients with overgrowth. Most of them, however, remain undetectable using banding karyotype analysis. In this study, we report on the analysis using a 1-Mb resolution array-based comparative genomic hybridization (CGH) of 93 patients with either a recognizable overgrowth condition (ie, Sotos syndrome or Weaver syndrome) or an unclassified overgrowth syndrome. Five clinically relevant imbalances (three duplications and two deletions) were identified and the pathogenicity of two additional anomalies (one duplication and one deletion) is discussed. Altered segments ranged in size from 0.32 to 18.2 Mb, and no recurrent abnormality was identified. These results show that array-CGH provides a high diagnostic yield in patients with overgrowth syndromes and point to novel chromosomal regions associated with these conditions. Although chromosomal deletions are usually associated with growth retardation, we found that the majority of the imbalances detected in our patients are duplications. Besides their importance for diagnosis and genetic counseling, our results may allow to delineate new contiguous gene syndromes associated with overgrowth, pointing to new genes, the deregulation of which may be responsible for growth defect.

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References

Redon R, Baujat G, Sanlaville D, Le Merrer M, Vekemans M, Munnich A . Interstitial 9q22.3 microdeletion: clinical and molecular characterisation of a newly recognised overgrowth syndrome. Eur J Hum Genet. 2006; 14(6):759-67. DOI: 10.1038/sj.ejhg.5201613. View

Lugtenberg D, Kleefstra T, Oudakker A, Nillesen W, Yntema H, Tzschach A . Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy. Eur J Hum Genet. 2008; 17(4):444-53. PMC: 2986218. DOI: 10.1038/ejhg.2008.208. View

Baujat G, Rio M, Rossignol S, Sanlaville D, Lyonnet S, Le Merrer M . Clinical and molecular overlap in overgrowth syndromes. Am J Med Genet C Semin Med Genet. 2005; 137C(1):4-11. DOI: 10.1002/ajmg.c.30060. View

Weksberg R, Smith A, Squire J, Sadowski P . Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development. Hum Mol Genet. 2003; 12 Spec No 1:R61-8. DOI: 10.1093/hmg/ddg067. View

Hannes F, Sharp A, Mefford H, de Ravel T, Ruivenkamp C, Breuning M . Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant. J Med Genet. 2008; 46(4):223-32. PMC: 2658752. DOI: 10.1136/jmg.2007.055202. View

Baujat G, Rio M, Rossignol S, Sanlaville D, Lyonnet S, Le Merrer M . Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome. Am J Hum Genet. 2004; 74(4):715-20. PMC: 1181947. DOI: 10.1086/383093. View

Romana S, Cherif D, Le Coniat M, Derre J, Flexor M, Berger R . In situ hybridization to interphase nuclei in acute leukemia. Genes Chromosomes Cancer. 1993; 8(2):98-103. DOI: 10.1002/gcc.2870080206. View

Partington M, Fagan K, Soubjaki V, Turner G . Translocations involving 4p16.3 in three families: deletion causing the Pitt-Rogers-Danks syndrome and duplication resulting in a new overgrowth syndrome. J Med Genet. 1997; 34(9):719-28. PMC: 1051054. DOI: 10.1136/jmg.34.9.719. View

Cole T, Hughes H . Sotos syndrome: a study of the diagnostic criteria and natural history. J Med Genet. 1994; 31(1):20-32. PMC: 1049594. DOI: 10.1136/jmg.31.1.20. View

10.

Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T . Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet. 2002; 30(4):365-6. DOI: 10.1038/ng863. View

11.

Moreno E, Basler K . dMyc transforms cells into super-competitors. Cell. 2004; 117(1):117-29. DOI: 10.1016/s0092-8674(04)00262-4. View

12.

Phelan M, Rogers R, Saul R, Stapleton G, Sweet K, McDermid H . 22q13 deletion syndrome. Am J Med Genet. 2001; 101(2):91-9. DOI: 10.1002/1096-8628(20010615)101:2<91::aid-ajmg1340>3.0.co;2-c. View

13.

Del Gaudio D, Fang P, Scaglia F, Ward P, Craigen W, Glaze D . Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males. Genet Med. 2006; 8(12):784-92. DOI: 10.1097/01.gim.0000250502.28516.3c. View

14.

Marcelis C, Hol F, Graham G, Rieu P, Kellermayer R, Meijer R . Genotype-phenotype correlations in MYCN-related Feingold syndrome. Hum Mutat. 2008; 29(9):1125-32. DOI: 10.1002/humu.20750. View

15.

Van Esch H, Hollanders K, Badisco L, Melotte C, Van Hummelen P, Vermeesch J . Deletion of VCX-A due to NAHR plays a major role in the occurrence of mental retardation in patients with X-linked ichthyosis. Hum Mol Genet. 2005; 14(13):1795-803. DOI: 10.1093/hmg/ddi186. View

16.

Tatton-Brown K, Pilz D, Orstavik K, Patton M, Barber J, Collinson M . 15q overgrowth syndrome: a newly recognized phenotype associated with overgrowth, learning difficulties, characteristic facial appearance, renal anomalies and increased dosage of distal chromosome 15q. Am J Med Genet A. 2009; 149A(2):147-54. DOI: 10.1002/ajmg.a.32534. View

17.

Orrico A, Galli L, Buoni S, Orsi A, Vonella G, Sorrentino V . Novel PTEN mutations in neurodevelopmental disorders and macrocephaly. Clin Genet. 2008; 75(2):195-8. DOI: 10.1111/j.1399-0004.2008.01074.x. View

18.

Blumenthal G, Dennis P . PTEN hamartoma tumor syndromes. Eur J Hum Genet. 2008; 16(11):1289-300. PMC: 6939673. DOI: 10.1038/ejhg.2008.162. View

19.

Faivre L, Gosset P, Cormier-Daire V, Odent S, Amiel J, Giurgea I . Overgrowth and trisomy 15q26.1-qter including the IGF1 receptor gene: report of two families and review of the literature. Eur J Hum Genet. 2002; 10(11):699-706. DOI: 10.1038/sj.ejhg.5200879. View

20.

Rio M, Clech L, Amiel J, Faivre L, Lyonnet S, Le Merrer M . Spectrum of NSD1 mutations in Sotos and Weaver syndromes. J Med Genet. 2003; 40(6):436-40. PMC: 1735492. DOI: 10.1136/jmg.40.6.436. View