Abstract
BackgroundChromosome 6pter-p24 deletion syndrome (OMIM #612582) is a recognized chromosomal disorder. Most of the individuals with this syndrome carry a terminal deletion of the short arm of chromosome 6 (6p) with a breakpoint within the 6p25.3p23 region. An approximately 2.1 Mb terminal region has been reported to be responsible for some major features of the syndrome. The phenotypic contributions of other deleted regions are unknown. Interstitial deletions of the region are uncommon, and reciprocal interstitial duplication in this region is extremely rare.Case presentationWe present a family carrying an interstitial deletion and its reciprocal duplication within the 6p25.1p24.3 region. The deletion is 5.6 Mb in size and was detected by array comparative genomic hybridization (aCGH) in a 26-month-old female proband who presented speech delay and mild growth delay, bilateral conductive hearing loss and dysmorphic features. Array CGH studies of her family members detected an apparently mosaic deletion of the same region in the proband’s mildly affected mother, but a reciprocal interstitial duplication in her phenotypically normal brother. Further chromosomal and fluorescence in situ hybridization (FISH) analyses revealed that instead of a simple mosaic deletion of 6p25.1p24.3, the mother actually carries three cell populations in her peripheral blood, including a deletion (~70 %), a duplication (~8 %) and a normal (~22 %) populations. Therefore, both the deletion and duplication seen in the siblings were apparently inherited from the mother.ConclusionsInterstitial deletion within the 6p25.1p24.3 region and its reciprocal duplication may co-exist in the same individual and/or family due to mitotic unequal sister chromatid exchange. While the deletion causes phenotypes reportedly associated with the chromosome 6pter-p24 deletion syndrome, the reciprocal duplication may have no or minimal phenotypic effect, suggesting possible triploinsensitivity of the same region. In addition, the cells with the duplication may compensate the phenotypic effect of the cells with the deletion in the same individual as implied by the maternal karyotype and her mild phenotype. Chromosomal and FISH analyses are essential to verify abnormal cytogenomic array findings.
Highlights
Chromosome 6pter-p24 deletion syndrome (OMIM #612582) is a recognized chromosomal disorder
While the deletion causes phenotypes reportedly associated with the chromosome 6pter-p24 deletion syndrome, the reciprocal duplication may have no or minimal phenotypic effect, suggesting possible triploinsensitivity of the same region
We present here the phenotypic and genomic findings in a family with an affected female proband who carries an interstitial deletion within the 6p25.1p24.3 region, her phenotypically unaffected brother with a reciprocal interstitial duplication of the same region, and their mosaic carrier mother who carries three cell populations with the deletion, the duplication and normal cells, respectively
Summary
Chromosome 6pter-p24 deletion syndrome (OMIM #612582) is a recognized chromosomal disorder. We present here the phenotypic and genomic findings in a family with an affected female proband who carries an interstitial deletion within the 6p25.1p24.3 region, her phenotypically unaffected brother with a reciprocal interstitial duplication of the same region, and their mosaic carrier mother who carries three cell populations with the deletion, the duplication and normal cells, respectively. This rare family provided an excellent opportunity to investigate the genomic etiology and genotypephenotype correlation of the chromosome 6pter-p24 deletion syndrome.
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