Elsevier

European Journal of Medical Genetics

Volume 51, Issue 6, November–December 2008, Pages 651-657
European Journal of Medical Genetics

Chromosomal imbalance letter
A 8.26 Mb deletion in 6q16 and a 4.95 Mb deletion in 20p12 including JAG1 and BMP2 in a patient with Alagille syndrome and Wolff–Parkinson–White syndrome

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Abstract

We report a child presenting with Alagille and Wolff–Parkinson–White (WPW) syndromes. Standard karyotyping showed a de novo 46,XY,t(1;6)(p31;q16) translocation. Fluorescent in situ hybridization analysis identified a de novo deletion in the 20p12 chromosomal region encompassing JAG1, the major gene responsible for Alagille syndrome. The aberration was further characterized using an Agilent 44K oligonucleotide array, which confirmed the 4.95 Mb 20p12 deletion. An additional 8.26 Mb deletion was identified at the 6q16 translocation breakpoint.

To our knowledge, WPW has never been associated with Alagille syndrome. The patient we describe presented with a 6q16 deletion containing 21 genes but no good candidate genes for WPW. The 20p12 deletion included 19 genes among them JAG1 and BMP2. Recently, two unrelated patients with WPW and BMP2 deletions have been reported. Despite a relationship between WPW and JAG1 deletion cannot be excluded, the JAG1 deletion is unlikely responsible for the ventricular preexcitation since WPW has never been associated with Alagille syndrome. Among the other deleted genes in 20p12, BMP2 appears to be a good candidate responsible for the WPW.

Section snippets

Chromosomal anomaly

Karyotyping based on RTG-banding was performed using standard methods on metaphases from peripheral blood of the patient and his parents. The cytogenetic analysis performed on the patient was 46,XY,t(1;6)(p31;q16) at ISCN +550 bands. Karyotypes were normal for both parents indicating an apparently balanced de novo translocation.

Fluorescent in situ hybridization (FISH) analysis using the RP5-1099D15 BAC probe encompassing the JAG1 gene identified a deletion in the 20p12 chromosomal region (Fig. 1

Clinical description

The patient was the second child of healthy unrelated parents with no remarkable familial medical history. At the time of delivery, mother and father were 29 and 31 years old, respectively. The older sister was healthy. Delivery was normal following an uncomplicated pregnancy. Birth weight was 2950 g (−2 SD), length 49 cm (−1 SD) and OFC 35.5 cm (0 SD). At 6 months of age, the patient was referred to our Medical Genetic Department because of facial dysmorphism and congenital heart defect. Physical

Discussion

We report a child suffering from WPW and Alagille syndromes. Molecular cytogenetic analyses showed two independent de novo deletions in 20p12 and 6q16. The 20p12 deletion encompasses the BMP2 and JAG1 genes.

Alagille syndrome (MIM118450) is a rare autosomal dominant condition including at least three of these five main features: paucity of intrahepatic bile ducts, congenital heart defects, skeletal defects, ocular anomalies, and a characteristic facies. It is a genetically heterogeneous disorder

Acknowledgments

We gratefully thank Rémi Houlgatte and Catherine Chevalier from Ouest Genopôle de Nantes, France.

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