The new Wolf–Hirschhorn syndrome critical region (WHSCR-2): A description of a second case

Authors

  • Laura Rodríguez,

    Corresponding author
    1. Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC) del Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain
    • CIAC, Instituto de Salud Carlos III, Sinesio Delgado 6, Pabellón 6, 28029 Madrid, Spain.
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  • Marcella Zollino,

    1. Istituto di Genetica Medica, Universitá Católica Sacro Cuore, Rome, Italy
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  • Salvador Climent,

    1. Departamento de Pediatría del Hospital de Ontinyent, Valencia, Spain
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  • Elena Mansilla,

    1. Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC) del Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain
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  • Fermina López-Grondona,

    1. Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC) del Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain
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  • María Luisa Martínez-Fernández,

    1. Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC) del Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain
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  • Marina Murdolo,

    1. Istituto di Genetica Medica, Universitá Católica Sacro Cuore, Rome, Italy
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  • María Luisa Martínez-Frías

    1. Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid, Spain
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Abstract

The Wolf–Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called “WHSCR-2” [Zollino et al., 2003]. © 2005 Wiley-Liss, Inc.

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