Genotype-phenotype correlation in four 15q24 deleted patients identified by array-CGH

Abstract

Microdeletion 15q24 is an emerging syndrome recently described, mainly due to increased use of array-CGH. Clinical features associate mild to moderate developmental delay, typical facial characteristics (high forehead and frontal hairline, broad eyebrows, downslanting palpebral features, long philtrum), hands (particularly proximal implanted thumbs) and genital anomalies (micropenis, hypospadias). We report here on four de novo cases having 2.5-6.1 Mb deletions involving 15q24: one 15q23q24.2 (Patient 1) and three 15q24.1q24.2 deletions (Patients 2-4). We correlate phenotype to genotype according to molecular boundaries of these deletions. Since bilateral iris coloboma and severe ano-rectal malformation were only present in Patient 1, we could link these anomalies to haploinsufficiency of 15q23 genes. Neither hypospadias nor micropenis were present in Patient 3 bearing the smallest deletion, therefore we could define 500 kb 15q24.1 region linked to these anomalies.

Figure 1

Facial characteristics of the 4 patients. A: Patient 1. B: Patient 2. C: Patient 3. D: Patient 4. Note high and large forehead on patients 1, 2 and 4.

Figure 2

Schematic representation of 15q24 rearrangements published cases characterized by array-CGH with their respective breakpoints and recurrent breakpoints BP1, BP2 and BP3 (Sharp and others 2007). Our four cases are also represented and segmental duplications featured. Recurrent breakpoint 4 (BP4) is also represented (Masurel-Paulet and others 2009). Three of our patients’ deletions have BP4 as proximal breakpoint.