Fine mapping of breakpoints in two unrelated patients with rare overlapping interstitial deletions of 9q with mild dysmorphic features

Abstract

Approximately, 20 cases of interstitial deletions of 9q have been reported in the literature spanning the breakpoints from 9q21 to 9q34. Unlike the 9q subtelomeric deletions, the interstitial deletions do not demonstrate a specific recognizable phenotype, although the majority of patients had microcephaly. Lack of precise molecular delineation of the extent of deletions in the published cases makes it difficult to develop an accurate genotype-phenotype correlation. We report on fine mapping of breakpoints using the Affymetrix Human Mapping 500K Array Set in two unrelated female patients with overlapping de novo deletion in 9q. SNP oligonucleotide microarray analysis (SOMA) indicated these to be relatively large deletions with Patient 1 having a 6.47 Mb deletion (>60 genes) spanning 9q32-q33.2 and Patient 2 having a 9.68 Mb deletion (>20 genes) localized to 9q31.1-q33.1. FISH analysis with BAC clones localized to the breakpoints showed discrepant results in Patient 1. Based on the review of previously reported interstitial 9q deletion patients and our patients, the minimal region of overlap (MRO) appears to encompass the 9q32 region and a phenotype characterized by microcephaly, neurological dysfunction and facial dysmorphism can be deduced. Our study shows the investigative nature of the latest array technology and the limitations of this technology in the accurate delineation of breakpoints.

The rewards and challenges of array-based karyotyping for clinical oncology applications

“…The end product does not yet have a consistent name and has been called virtual karyotyping, 2,3 digital karyotyping, 4 molecular allelokaryotyping 5 and molecular karyotyping. 6 Other terms used to describe the arrays used for karyotyping include SOMA (SNP oligonucleotide microarrays) 7 and CMA (chromosome microarray). 8,9 Some consider all platforms to be a type of array comparative genomic hybridization (arrayCGH), whereas others reserve that term for two-dye methods, and still others who segregate SNP arrays because they generate more and different information than two-dye arrayCGH methods.…”

Prenatal Diagnosis of a Female Fetus with Ring Chromosome 9, 46,XX,r(9)(p24q34), and a de novo Interstitial 9p Deletion

“…In this way, EHMT1 is one of the genes responsible for brain development with a determinant role in chromatin remodeling [Stewart and Kleefstra, 2007;Kleefstra et al, 2009]. Unlike the 9q subtelomeric deletions, the interstitial ones do not demonstrate a specific and recognizable phenotype apart from microcephaly; 20 cases have been reported in the literature spanning the breakpoints from 9q21 to 9q34 with an imprecise molecular delineation of the extent of the deletions [Kulharya et al, 2008]. As far as this case is concerned, an unspecific phenotype known as 'ring chromosome phenotype' must be expected at a prenatal level, defined by clinical characteristics of r(9) and extra features of deletion 9q or deletion 9q syndrome.…”

Patients Carrying 9q31.1-q32 Deletion Share Common Features with Cornelia de Lange Syndrome

“…A comparison of our patient with the 11 previously reported cases with partially overlapping deletions is provided in Table 2 and their deletion regions are compared in Fig. 5 (case 1 and case 4 came from DECIPHER, http://decipher.sanger.ac.uk/) [10,11,12,13,14,15,16]. …”

“…hg19. The base pairs of case 6[13], case 7[14] and case 8[14] were estimated according to 106.2-113.27Mb, 111,330,304-121,013,839, and 115,369,807-121,843,479 based on NCBI36/hg18. Case 9[15] and Case 10[16].…”