Two siblings with alternate unbalanced recombinants derived from a large cryptic maternal pericentric inversion of chromosome 20

Abstract

Two brothers, with dissimilar clinical features, were each found to have different abnormalities of chromosome 20 by subtelomere fluorescence in situ hybridization (FISH). The proband had deletion of 20p subtelomere and duplication of 20q subtelomere, while his brother was found to have a duplication of 20p subtelomere and deletion of 20q subtelomere. Parental cytogenetic studies were initially thought to be normal, both by G-banding and by subtelomere FISH analysis. Since chromosome 20 is a metacentric chromosome and an inversion was suspected, we used anchored FISH to assist in identifying a possible inversion. This approach employed concomitant hybridization of a FISH probe to the short (p) arm of chromosome 20 with the 20q subtelomere probe. We identified a cytogenetically non-visible, mosaic pericentric inversion of one of the maternal chromosome 20 homologues, providing a mechanistic explanation for the chromosomal abnormalities present in these brothers. Array comparative genomic hybridization (CGH) with both a custom-made BAC and cosmid-based subtelomere specific array (TEL array) and a commercially-available SNP-based array confirmed and further characterized these rearrangements, identifying this as the largest pericentric inversion of chromosome 20 described to date. TEL array data indicate that the 20p breakpoint is defined by BAC RP11-978M13, ~900 kb from the pter; SNP array data reveal this breakpoint to occur within BAC RP11-978M13. The 20q breakpoint is defined by BAC RP11-93B14, ~1.7 Mb from the qter, by TEL array; SNP array data refine this breakpoint to within a gap between BACs on the TEL array (i.e. between RP11-93B14 and proximal BAC RP11-765G16).

Molecular analysis of ring chromosome 20 syndrome reveals two distinct groups of patients

“…There are no known haploinsufficient genes in these deletions, besides the previously discussed candidate genes ( CHRNA4 and KCNQ2 ). While these additional clinical findings cannot be directly linked to any known disease genes within these deleted regions, similar phenotypic findings have been reported in patients with deletions of the sub-telomeric regions of chromosome 20 30. These findings include intellectual disability, developmental delays (including speech delay), mild dysmorphic features, short stature, hypotonia, and epilespsy.…”

A Case of Partial Trisomy 20p Resulting from Meiotic Recombination of a Maternal Pericentric Inversion

“…To our knowledge, this is the 4th report in the world and the 1st one in Korea of a patient with rec(20)dup(20p) [2-4]. …”

Duplication of 20qter and deletion of 20pter due to paternal pericentric inversion: Patient report and review of 20qter duplications

“…The duplications of all of these patients are considerably smaller than the 19.5 Mb duplication of terminal 20q seen in our patient. One male patient was reported with a deletion of the terminal 900 kb of chromosome 20p and a 1.7 Mb duplication of terminal 20q with developmental delay, speech delay, and some autistic behaviors [DeScipio et al, 2009]. He was noted to have normal intrauterine growth, mild synophrys, long eyelashes, arched/thick eyebrows, mild hirsutism, slightly posteriorly rotated ears with thickened superior helices, a thin upper lip, and multiple sacral dimples.…”