FOXC1 haploinsufficiency due to 6p25 deletion in a patient with rapidly progressing aortic valve disease

Caroline Ovaert (1, 2) , Tiffany Busa (1, 2) , Emilie Faure (1) , Chantal Missirian (1, 2) , Nicole Philip (1, 3) , Florent Paoli , Mathieu Milh (1, 3) , Loic Mace , Stéphane Zaffran (1)

1 GMGF - Génétique Médicale et Génomique Fonctionnelle
2 Département de génétique médicale [Hôpital de la Timone - APHM]
3 Service de pédiatrie et neurologie pédiatrique

6p25 deletion is a rare but well-known entity. The main clinical features include an abnormal facial appearance, developmental delay, and ocular anomalies. Cardiac anomalies are frequently seen but remain poorly delineated. We describe a 4-year-old girl with 6p25.3 deletion, which includes the FOXC1 gene, typical dysmorphic features associated with developmental delay and oculo-motor anomalies. Aortic valve dysplasia was diagnosed early in life. The cardiac lesion progressed very rapidly between the age of 3 and 4 years requiring aortic valve replacement. Genomic analysis of blood and excised valve tissue showed down-regulation of FOXC1 but also FOXC2 expression in the diseased aortic valve. This allows us to speculate on the potential role of FOXC1 in aortic valve anomalies.

Mots clés: 6p25 deletion; aortic valve disease; FOXC1; genetics

Domaines: Génétique humaine

Caroline Ovaert, Tiffany Busa, Emilie Faure, Chantal Missirian, Nicole Philip, et al.. FOXC1 haploinsufficiency due to 6p25 deletion in a patient with rapidly progressing aortic valve disease. American Journal of Medical Genetics Part A, 2017, 173 (9), pp.2489-2493. ⟨10.1002/ajmg.a.38331⟩. ⟨hal-01741720⟩