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

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. División de Genética, CIBO, Instituto Mexicano del Seguro Social, Sierra Mojada 800, CP 44340 , Guadalajara, México

    Azubel Ramírez-Velazco, Thania Alejandra Aguayo-Orozco, Luis Figuera, Horacio Rivera, Patricio Barros-Núñez, Ingrid Patricia Dávalos-Rodríguez, José Elías García-Ortiz & María G. Domínguez

  2. Doctorado en Genética Humana, CUCS, Universidad de Guadalajara, Sierra Mojada 950, CP 44340, Guadalajara, México

    Azubel Ramírez-Velazco, Thania Alejandra Aguayo-Orozco, Luis Figuera, Horacio Rivera & Ingrid Patricia Dávalos-Rodríguez

  3. División de Inmunología, CIBO, Instituto Mexicano del Seguro Social, Sierra Mojada 800, CP 44340 , Guadalajara, México

    Luis Jave-Suárez & Adriana Aguilar-Lemarroy

  4. Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara, Sierra Mojada 950, CP 44340 , Guadalajara, México

    Luis A. Torres-Reyes

  5. Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey , 64460, Nuevo León, México

    Carlos Córdova-Fletes

  6. Departamento de Cardiología, Hospital de Pediatría, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Salvador Quevedo y Zubieta 724, CP 44360 , Guadalajara, México

    Saturnino Delgadillo-Pérez

Authors
  1. Azubel Ramírez-Velazco
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  2. Thania Alejandra Aguayo-Orozco
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  3. Luis Figuera
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  4. Horacio Rivera
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  5. Luis Jave-Suárez
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  6. Adriana Aguilar-Lemarroy
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  7. Luis A. Torres-Reyes
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  8. Carlos Córdova-Fletes
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  9. Patricio Barros-Núñez
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  10. Saturnino Delgadillo-Pérez
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  11. Ingrid Patricia Dávalos-Rodríguez
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  12. José Elías García-Ortiz
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  13. María G. Domínguez
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Corresponding author

Correspondence to María G. Domínguez.

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Corresponding editor: Indrajit Nanda

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Ramírez-Velazco, A., Aguayo-Orozco, T.A., Figuera, L. et al. Williams–Beuren syndrome in Mexican patients confirmed by FISH and assessed by aCGH. J Genet 98, 34 (2019). https://doi.org/10.1007/s12041-019-1080-7

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  • DOI: https://doi.org/10.1007/s12041-019-1080-7

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