BACKGROUND: The Wolf-Hirschhorn syndrome (WHS) is usually caused by terminal deletions of the short arm of chromosome 4 and is phenotypically defined by growth and mental retardation, seizures, and specific craniofacial manifestations. Large variation is observed in phenotypic expression of these features. In order to compare the phenotype with the genotype, we localised the breakpoints of the 4 pter aberrations using a chromosome 4 specific tiling BAC/PAC array. METHODS: In total, DNA from 21 patients was analysed, of which 8 had a cytogenetic visible and 13 a submicroscopic deletion. RESULTS AND CONCLUSION: In addition to classical terminal deletions sized between 1.9 and 30 Mb, we observed the smallest terminal deletion (1.4 Mb) ever reported in a patient with mild WHS stigmata. In addition, we identified and mapped interstitial deletions in four patients. This study positions the genes causing microcephaly, intrauterine and postnatal growth retardation between 0.3 and 1.4 Mb and further refines the regions causing congenital heart disease, cleft lip and/or palate, oligodontia, and hypospadias.
BACKGROUND: The Wolf-Hirschhorn syndrome (WHS) is usually caused by terminal deletions of the short arm of chromosome 4 and is phenotypically defined by growth and mental retardation, seizures, and specific craniofacial manifestations. Large variation is observed in phenotypic expression of these features. In order to compare the phenotype with the genotype, we localised the breakpoints of the 4 pter aberrations using a chromosome 4 specific tiling BAC/PAC array. METHODS: In total, DNA from 21 patients was analysed, of which 8 had a cytogenetic visible and 13 a submicroscopic deletion. RESULTS AND CONCLUSION: In addition to classical terminal deletions sized between 1.9 and 30 Mb, we observed the smallest terminal deletion (1.4 Mb) ever reported in a patient with mild WHS stigmata. In addition, we identified and mapped interstitial deletions in four patients. This study positions the genes causing microcephaly, intrauterine and postnatal growth retardation between 0.3 and 1.4 Mb and further refines the regions causing congenital heart disease, cleft lip and/or palate, oligodontia, and hypospadias.
Authors: Peter Hammond; Femke Hannes; Michael Suttie; Koen Devriendt; Joris Robert Vermeesch; Francesca Faravelli; Francesca Forzano; Susan Parekh; Steve Williams; Dominic McMullan; Sarah T South; John C Carey; Oliver Quarrell Journal: Eur J Hum Genet Date: 2011-07-27 Impact factor: 4.246
Authors: Patricia L Heard; Erika M Carter; Analisa C Crandall; Courtney Sebold; Daniel E Hale; Jannine D Cody Journal: Am J Med Genet A Date: 2009-07 Impact factor: 2.802
Authors: Erica F Andersen; John C Carey; Dawn L Earl; Deyanira Corzo; Michael Suttie; Peter Hammond; Sarah T South Journal: Eur J Hum Genet Date: 2013-08-21 Impact factor: 4.246
Authors: Hannelie Engbers; Jasper J van der Smagt; Ruben van 't Slot; Joris R Vermeesch; Ron Hochstenbach; Martin Poot Journal: Eur J Hum Genet Date: 2008-10-01 Impact factor: 4.246