Unintended Diagnosis of Von Hippel Lindau Syndrome Using Array Comparative Genomic Hybridization (CGH): Counseling Chall
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CASE PRESENTATION
Unintended Diagnosis of Von Hippel Lindau Syndrome Using Array Comparative Genomic Hybridization (CGH): Counseling Challenges Arising from Unexpected Information Jennifer Hogan & A. Turner & K. Tucker & L. Warwick
Received: 4 October 2011 / Accepted: 14 June 2012 / Published online: 16 August 2012 # National Society of Genetic Counselors, Inc. 2012
Abstract Array Comparative Genomic Hybridization (array CGH) is a powerful tool for identifying genomic imbalances and providing a diagnosis in individuals with a normal karyotype. It has been particularly useful in the investigation of individuals with developmental delay +/−, dysmorphic features and/or multiple congenital abnormalities. However, this non-targeted method of scanning the whole genome can reveal unexpected information. We present a case where array CGH identified the cause of a proband’s moderate mental retardation by discovery of a de novo deletion of chromosome 3p25.3. This deletion was shown to contain at least 25 genes including the VHL gene, the deletion or mutation of which leads to Von Hippel Lindau (VHL) syndrome. Presymptomatic testing for VHL is usually offered after appropriate genetic counseling about the implications of this condition. Therefore, scanning the genome by array CGH presents a number of challenges for the genetic counselor. We suggest that further understanding of the psychosocial effects of array CGH is needed in order for appropriate pre- and post-test counseling to be provided.
J. Hogan : A. Turner : K. Tucker : L. Warwick ACT Genetic Service The Canberra Hospital, Canberra, ACT, Australia A. Turner Department of Medical Genetics, Sydney Children’s Hospital, Sydney, NSW, Australia K. Tucker Hereditary Cancer Clinic, Prince of Wales Hospital, Sydney, NSW, Australia J. Hogan (*) ACT Genetics Service, PO BOX 11, Woden, ACT 2606, Australia e-mail: [email protected]
Keywords Array Comparative Genomic Hybridization . Array CGH . Von Hippel Lindau Syndrome . Unexpected diagnosis . Chromosomal abnormality
Introduction Array Comparative Genomic Hybridization (CGH) is a powerful tool for identifying genomic imbalances and providing a diagnosis in individuals who have previously had a normal karyotype (Vermeer et al. 2007). It has been particularly useful in the investigation of individuals with developmental delay +/−, dysmorphic features and/or multiple congenital abnormalities (Lu et al. 2007). Array CGH has allowed the discovery of new genes and characterisation of genetic syndromes and is a routine test which is replacing the use of karyotyping (Darilek et al. 2008; Fruhman and Van den Veyver 2010). This technology allows for detection of aneuploidies, deletions and duplications, along with unbalanced chromosomal rearrangements (Lu et al. 2007). A key benefit of array CGH is it’s higher resolution; 50–100 kb as compared to 5 Mb for karyotyping (Fruhman and Van den Veyver 2010). It allows for simultaneous examination of multiple disease-causing loci as well as identification of novel chromosomal abnormal
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