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.

Maturation of cortical circuits requires Semaphorin 7A

“…The proper establishment of such organized connectivity is critical for normal sensory function (11). In humans, microdeletions in chromosome 15q24, which include SEMA7A, are associated with a syndrome characterized by autism, developmental delay, and abnormalities in somatosensation (12)(13)(14). Together, these data suggest that Sema7A may contribute critically to the establishment and functional maturation of patterned synaptic circuits.…”

Deletion and duplication of 15q24: Molecular mechanisms and potential modification by additional copy number variants

“…1, Table 1). 23 Two patients exhibiting cognitive impairment, skeletal deformities, and dysmorphic facial features have been reported to have 15q24 duplications whose breakpoints localized to the LCR regions and include an SRO of ϳ1.2 Mb, which is reciprocal to that of the 15q24 deletions ( Fig. 1, Table 2).…”

An Additional Case of the Recurrent 15q24.1 Microdeletion Syndrome and Review of the Literature

“…To date there are 18 reported cases involving 15q24.1 deletion which are detected by array-based methods (Andrieux et al, 2009;El-Hattab et al, 2009;El-Hattab et al, 2010;Klopocki et al, 2008;Marshall et al, 2008;Masurel-Paulet et al, 2009;McInnes et al, 2010;Sharp et al, 2007;Van Esch et al, 2009). The sizes of the deleted regions range from 1.7 Mb to 6.1 Mb.…”

“…Fifteen of the cases had the proximal breakpoints within 15q24.1, while the starting points of the deletion of the remaining three cases were more centromeric. For the latter group, two cases from different ASD cohorts (Marshall et al, 2008;McInnes et al, 2010) had deletions starting from 69,601,300 and 69,897,977; while another case (deceased at 25 months) had the start of the breakpoint at 67,807,119 (Andrieux et al, 2009). The last patient also had the biggest deletion of 6.1 Mb.…”