Chromosomal imbalance letterA 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
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.
References (12)
- et al.
NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the NOTCH signalling pathway
Am. J. Hum. Genet.
(2006) - et al.
An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation
Cell
(2007) - et al.
Bmp2 instructs cardiac progenitors to form the heart-valve-inducing field
Dev. Biol.
(2006) - et al.
Interstitial 6q deletion: clinical and array CGH characterisation of a new patient
Eur. J. Med. Genet.
(2005) - et al.
Jagged1 mutations in alagille syndrome
Hum. Mutat.
(2001) - et al.
Identification of a gene responsible for familial Wolff–Parkinson–White syndrome
N. Engl. J. Med.
(2001)