Research article

Array-CGH in patients with Kabuki-like phenotype: Identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration

Ivon Cuscó^1,2 , Miguel del Campo^1,2,3 , Mireia Vilardell^1,2 , Eva González⁴ , Blanca Gener^1,5 , Enrique Galán⁶ , Laura Toledo⁷ and Luis A Pérez-Jurado^1,2,3

¹Unitat de Genètica, Universitat Pompeu Fabra, Barcelona, Spain

²CIBER de enfermedades raras (CIBERER), Barcelona, Spain

³Programa de Medicina Molecular y Genética, Hospital Vall d'Hebron, Barcelona, Spain

⁴Centre de Regulació Genòmica (CRG), Barcelona, Spain

⁵Clinical Genetics Unit, Hospital de Cruces, Barakaldo, Bizkaia, Spain

⁶Hospital Infanta Cristina, Badajoz, Spain

⁷Hospital Materno Infantil, Unidad de Neurologia Infantil, Las Palmas de Gran Canaria, Spain

author email corresponding author email

BMC Medical Genetics 2008, 9:27doi:10.1186/1471-2350-9-27

Published:	11 April 2008

Abstract

Background

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown.

Methods

We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited.

Results

No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group.

Conclusion

Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.