Research

8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families

John CK Barber^1,2,3 , Dave Bunyan¹ , Merryl Curtis⁴ , Denise Robinson⁴ , Susanne Morlot⁵ , Anette Dermitzel⁵ , Thomas Liehr⁶ , Claudia Alves⁷ , Joana Trindade⁷ , Ana I Paramos⁸ , Clare Cooper⁹ , Kevin Ocraft⁹ , Emma-Jane Taylor¹ and Viv K Maloney¹

¹  Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, SP2 8BJ, UK

²  National Genetics Reference Laboratory (Wessex), Salisbury NHS Foundation Trust, Salisbury, SP2 8BJ, UK

³  Human Genetics Division, Southampton University School of Medicine, Southampton, SO16 6YD, UK

⁴  Institute of Medical Genetics, University Hospital Wales, Cardiff, CF14 4XW, UK

⁵  Medizinisches Versorgungszentrum wagnerstibbe, Georgstr 50, Hannover, Germany

⁶  Institut für Humangenetik und Anthropologie, Jena University Hospital, Jena, Germany

⁷  GDPN, Genetica Medica e Diagnostico Pre-natal, Porto, Portugal

⁸  Prenatal Diagnosis Unit, District Hospital, Faro, Portugal

⁹  Centre for Medical Genetics, Nottingham City Hospital, Nottingham, NG5 1PB, UK

author email corresponding author email

Molecular Cytogenetics 2010, 3:3doi:10.1186/1755-8166-3-3

Published:	18 February 2010

Abstract

Background

The 8p23.1 duplication syndrome and copy number variation of the 8p23.1 defensin gene cluster are cytogenetically indistinguishable but distinct at the molecular level. To our knowledge, the 8p23.1 duplication syndrome has been described at prenatal diagnosis only once and we report our experience with four further apparent duplications ascertained at prenatal diagnosis.

Methods

Additional material at band 8p23.1 was detected using conventional G-banded cytogenetics in each case. Multiplex Ligation-dependent Probe Amplification (MLPA) or Fluorescence In Situ Hybridisation (FISH) were used depending on whether only DNA (Cases 1 and 4) or cytogenetic preparations (Cases 2 and 3) were available from the laboratory of origin. The extent of the duplication in Case 1 was retrospectively determined using array Comparative Genomic Hybridisation (array CGH).

Results

Three cases of 8p23.1 duplication syndrome were found (Cases 1 to 3). Two were de novo and continued to term and the third, a paternally transmitted duplication, was terminated because of a previous child with psychomotor delay and 8p23.1 duplication syndrome. Case 1 was ascertained with a hypoplastic left heart but the ventricular septal and interventricular defects, in Cases 2 and 3 respectively, were found after ascertainment for advanced maternal age. By contrast, case 4 was a maternally transmitted copy number variation of the defensin cluster with normal outcome.

Conclusions

Our data underline the need to differentiate 8p23.1 duplications from copy number variation of the defensin cluster using FISH, MLPA or array CGH. Cardiac defects were ascertained by ultrasound in only one of the three duplication 8p23.1 pregnancies but were visible in two of the three at 21 to 22 weeks gestation. Our results provide further evidence that both deletion and duplication of the GATA4 transcription factor can give rise to a variety of conotruncal heart defects with variable penetrance and expressivity.