Array based characterization of a terminal deletion involving chromosome subband 15q26.2: an emerging syndrome associated with growth retardation, cardiac defects and developmental delay

Abstract

BackgroundSubtelomeric regions are gene rich and deletions in these chromosomal segments have been demonstrated to account for approximately 2.5% of patients displaying mental retardation with or without association of dysmorphic features. However, cases that report de novo terminal deletions on chromosome arm 15q are rare.MethodsIn this study we present the first example of a detailed molecular genetic mapping of a de novo deletion in involving 15q26.2-qter, caused by the formation of a dicentric chromosome 15, using metaphase FISH and tiling resolution (32 k) genome-wide array-based comparative genomic hybridization (CGH).ResultsAfter an initial characterization of the dicentric chromosome by metaphase FISH, array CGH analysis mapped the terminal deletion to encompass a 6.48 megabase (Mb) region, ranging from 93.86–100.34 Mb on chromosome 15.ConclusionIn conclusion, we present an additional case to the growing family of reported cases with 15q26-deletion, thoroughly characterized at the molecular cytogenetic level. In the deleted regions, four candidate genes responsible for the phenotype of the patient could be delineated: IGFR1, MEF2A, CHSY1, and TM2D3. Further characterization of additional patients harboring similar 15q-aberrations might hopefully in the future lead to the description of a clear cut clinically recognizable syndrome.

Recombinant Human Growth Hormone Therapy in Children with Chromosome 15q26 Deletion

“…Typical clinical features include growth retardation, developmental delay, microcephaly and cardiac defects. Our observations are in line with these and other previously reported clinical features such as craniofacial and limb deformities [3,4,5,6,7,11,12,13,14,15,16,17,18,19,20,21,22]. In our cohort, case 5 had congenital subglottic stenosis requiring tracheostomy, a new feature not described before.…”

“…Patients with terminal 15q26 deletions usually have loss of one copy of the IGFIR gene [3]. Typical clinical features include growth retardation, developmental delay, microcephaly and cardiac defects.…”

“…Deletion of the IGFIR gene is rare but is increasingly being reported due to the availability of detailed molecular genetic mapping such as microarray comparative genomic hybridisation (CGH) [3]. The response to GH therapy in these potentially GH-resistant children with very short stature is currently unclear [4,5,6,7].…”

Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities

“…Several published reports have examined smaller cohorts of patients with complex clinical presentations and described non-recurrent contiguous gene deletion syndromes contributing to CVMs, including 1p36 monosomy, 30 15q26 deletion, [31][32][33][34][35] Wolf-Hirschhorn syndrome (4p16.3 deletion), 36 Cri-du-chat syndrome (5p15.2 monosomy), 37 Miller-Dieker lissencephaly syndrome (17p13.3 deletion) 38 and 17q23.1q23.2 microdeletion syndrome. 18 Examples where such an approach was successful in identifying specific dosage-sensitive genes include JAG1 in Allagile Figure 1 Variable de novo (DN) deletions of 16q24.3 observed in multiple subjects with CVMs and ECAs.…”

Distal Trisomy of 10q with Distal Monosomy of 15q Due to a Paternal Translocation

“…Severe ocular issues, dysmorphism of limbs 25 All the 15qter deletion cases have presented with preand postnatal growth retardation; a 15q26.2➛15qter deletion causing prenatal growth retardation, i.e. low birth weight.…”