Journal of Genetics

, 98:34 | Cite as

Williams–Beuren syndrome in Mexican patients confirmed by FISH and assessed by aCGH

  • Azubel Ramírez-Velazco
  • Thania Alejandra Aguayo-Orozco
  • Luis Figuera
  • Horacio Rivera
  • Luis Jave-Suárez
  • Adriana Aguilar-Lemarroy
  • Luis A. Torres-Reyes
  • Carlos Córdova-Fletes
  • Patricio Barros-Núñez
  • Saturnino Delgadillo-Pérez
  • Ingrid Patricia Dávalos-Rodríguez
  • José Elías García-Ortiz
  • María G. DomínguezEmail author
Research Article


Williams–Beuren syndrome (WBS) has a prevalence of 1/7500–20000 live births and results principally from a de novo deletion in 7q11.23 with a length of 1.5 Mb or 1.8 Mb. This study aimed to determine the frequency of 7q11.23 deletion, size of the segment lost, and involved genes in 47 patients with a clinical diagnosis of WBS and analysed by fluorescence in situ hybridization (FISH); among them, 31 had the expected deletion. Micro-array comparative genomic hybridization (aCGH) confirmed the loss in all 18 positive-patients tested: 14 patients had a 1.5 Mb deletion with the same breakpoints at 7q11.23 (hg19: 72726578–74139390) and comprising 24 coding genes from TRIM50 to GTF2I. Four patients showed an atypical deletion: two had a 1.6 Mb loss encompassing 27 coding genes, from NSUN5 to GTF2IRD2; another had a 1.7 Mb deletion involving 27 coding genes, from POM121 to GTF2I; the remaining patient presented a deletion of 1.2 Mb that included 21 coding genes from POM121 to LIMK1. aCGH confirmed the lack of deletion in 5/16 negative-patients by FISH. All 47 patients had the characteristic facial phenotype of WBS and 45 of 47 had the typical behavioural and developmental abnormalities. Our observations further confirm that patients with a classical deletion present a typical WBS phenotype, whereas those with a high (criteria of the American Association of Pediatrics, APP) clinical score but lacking the expected deletion may harbour an ELN point mutation. Overall, the concomitant CNVs appeared to be incidental findings.


deletion 7q11.23 Williams–Beuren syndrome supra-valvular aortic stenosis micro-array comparative genomic hybridization fluorescence in situ hybridization 



We thank the patients and parents for their invaluable co-operation, in addition to MD. Ana I. Vázquez-Velásquez for technical support. This work was supported by FIS/IMSS/PROT/MD14/1352 del Instituto Mexicano del Seguro Social.


  1. Borg I., Delhanty J. D. A. and Baraitser M. 1995 Detection of hemizygosity at the elastin locus by FISH analysis as a diagnostic test in both classical and atypical cases of Williams syndrome. Med. Genet. 32, 692–696.CrossRefGoogle Scholar
  2. Collins R. T., Kaplan P., Somes G. W. and Rome J. J. 2010 Long-term out comes of patients with cardiovascular abnormalities and Williams syndrome. Am. J. Cardiol. 105, 874–878.CrossRefGoogle Scholar
  3. Committee on Genetics. 2001 American Academy of Pediatrics: health care supervision for children with Williams syndrome. Pediatrics 107, 1192–1204.Google Scholar
  4. Delio M., Pope K., Wang T., Samanich J., Haldeman-Englert C., Kaplan P. et al. 2013 Spectrum of elastin sequence variants and cardiovascular phenotypes in 49 patients with Williams–Beuren syndrome. Am. J. Med. Gen. A. 161, 527–533.CrossRefGoogle Scholar
  5. Dutra R. L., Honjo R. S., Kulikowski L. D., Fonseca F. M., Pieri P. C., Jehee F. S. et al. 2012 Copy number variation in Williams–Beuren syndrome: suitable diagnostic strategy for developing countries. BMC. Res. Notes 5, 13.CrossRefGoogle Scholar
  6. Ferrero G. B., Biamino E., Sorasio L., Banaudi E., Peruzzi L., Forzano B. et al. 2007 Presenting phenotype and clinical evaluation in a cohort of 22 Williams–Beuren syndrome patients. Eur. J. Med. Genet. 50, 327–337.CrossRefGoogle Scholar
  7. Ferrero G., Howald C., Micale L., Biamino E., Augello B., Fusco C. et al. 2010 An atypical 7q11.23 deletion in a normal IQ Williams–Beuren syndrome patient. Eur. J. Med. Genet. 18, 33–38.Google Scholar
  8. Jabbi M., Kippenhan J., Kohn P., Marenco S., Mervis C., Morris C. et al. 2012 The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function. Proc. Natl. Acad. Sci. USA 109, 860–866.CrossRefGoogle Scholar
  9. Kalis N. N., Sulaibikh L. K., Al Amer S. R. and Al Amer H. Y. 2017 Computerized tomography use in Williams–Beuren syndrome aortopathy. Heart Views 18, 21–25.CrossRefGoogle Scholar
  10. Kim Y., Cho J., Kang E., Kim G., Seo E., Lee B. et al. 2016 Endocrine dysfunctions in children with Williams–Beuren syndrome. Ann. Pediatr. Endocrinol Metab. 21, 15–20.CrossRefGoogle Scholar
  11. Li L., Huang L., Luo Y., Huang X., Lin S. and Fang Q. 2016 Differing microdeletion sizes and breakpoints in chromosome 7q11.23 in Williams–Beuren syndrome detected by chromosomal microarray analysis. Mol. Syndromol. 6, 268–275.CrossRefGoogle Scholar
  12. Lowery M. C., Morris C. A., Ewart A., Brothman L. J., Zhu X. L., Leonard C. et al. 1995 Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients. Am. J. Hum. Genet. 57, 49–53.PubMedPubMedCentralGoogle Scholar
  13. Merla G., Brunetti-Pierre N., Micale L. and Fusco C. 2010 Copy number variants at Williams–Beuren syndrome 7q11.23 region. Hum. Genet. 128, 3–26.CrossRefGoogle Scholar
  14. Metcalfe K., Rucka A. K., Smoot L., Hofstadler G., Tuzler G., McKeown P. et al. 2000 Elastin: mutational spectrum in supravalvular aortic stenosis. Eur. J. Hum. Genet. 8, 955–963.CrossRefGoogle Scholar
  15. Morris C. A. 2010 Introduction: Williams syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 154C, 203–208.CrossRefGoogle Scholar
  16. Nickerson E., Greenberg F., Keating M. T., Mc Caskill C. and Shaffer L. G. 1995 Deletions of the elastin gene at 7q11.23 occur in approximately 90% of patients with Williams syndrome. Am. J. Hum. Genet. 56, 1156–1161.PubMedPubMedCentralGoogle Scholar
  17. Pani A., Hobart H., Morris C., Mervis C., Bray-Ward P., Kimberley K. et al. 2010 Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams Syndrome. PLoS One 5, e12349.CrossRefGoogle Scholar
  18. Peddibhotla S., Nagamani S. C. S., Erez A., Hunter J. V., J Lloyd Holder J. L., Carlin M. E. et al. 2015 Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27. Eur. J. Hum. Genet. 23, 54–60.CrossRefGoogle Scholar
  19. Pober B. R., Lacro R. V., Rice C., Mandell V. and Teele R. L. 1993 Renal findings in 40 individuals with Williams syndrome. Am. J. Med. Genet. 46, 271–274.CrossRefGoogle Scholar
  20. Ramírez-Velazco A. 2017 Caracterización de la deleción 7q11.23 mediante FISH y aCGH en pacientes con síndrome Williams–Beuren. (Unpublished data from doctoral thesis). Ph.D. Program on Human Genetics, Universidad de Guadalajara, Guadalajara, México.Google Scholar
  21. Ramírez Velazco A. and Domínguez Quezada M. G. 2017 Atypical deletions in Williams–Beuren syndrome. Rev. Med. Inst. Mex. Seguro Soc. 55, 615–620.Google Scholar
  22. Rivera H., Vásquez-Velásquez A. I., Domínguez-Quezada M. G. and Ramírez-Velazco A. 2016 Two further triple-X/rea(X) females in an inv(X)(p22q22) family. J. Genet. 95, 157–159.CrossRefGoogle Scholar
  23. Rooney D. E. 2001 Human cytogenetics: constitutional analysis, 3rd edn, pp. 33–53. Oxford University Press, New York.Google Scholar
  24. Schubert C. 2009 The genomic basis of the Williams–Beuren syndrome. Cell Mol. Life Sci. 66, 1178–1197.CrossRefGoogle Scholar
  25. Watts C., Knutsen R., Ciliberto C. and Mecham R. 2011 Evidence for heterozygous abnormalities of the elastin gene (ELN) affecting the quantity of vocal fold elastic fibers: a pilot study. J. Voice 25, e85–e90.CrossRefGoogle Scholar
  26. Zhou L., Chen C., Li H., Chen Y., Xu X., Lin X. and Tang S. 2014 Delineation variable genotype/phenotype correlations of 6q27 terminal deletion derived from dic(6;18)(q27;p10). Mol. Cytogenet. 7, 78–85.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.División de Genética, CIBOInstituto Mexicano del Seguro SocialGuadalajaraMéxico
  2. 2.Doctorado en Genética Humana, CUCSUniversidad de GuadalajaraGuadalajaraMéxico
  3. 3.División de Inmunología, CIBOInstituto Mexicano del Seguro SocialGuadalajaraMéxico
  4. 4.Departamento de Biología Molecular y Genómica, CUCSUniversidad de GuadalajaraGuadalajaraMéxico
  5. 5.Departamento de Bioquímica y Medicina Molecular, Facultad de MedicinaUniversidad Autónoma de Nuevo LeónMonterrey México
  6. 6.Departamento de Cardiología, Hospital de Pediatría, Centro Médico Nacional de OccidenteInstituto Mexicano del Seguro SocialGuadalajaraMéxico

Personalised recommendations