A new neocentromere locus on chromosome 13 resulting in mosaic tetrasomy for distal 13q and an asymmetric phenotype

Abstract

An 8-year-old girl was referred to the Genetics Centre with mild developmental delay, mild dysmorphic features, and a head circumference on the 98th centile. She was noted to have large irregular ear lobes, torticollis, and mild hemihypertrophy. Karyotype analysis of cultured peripheral lymphocytes and skin fibroblasts revealed the presence of a symmetrical supernumerary marker chromosome in 13% of cells from both tissue types. Further analysis showed that this marker chromosome originated from the distal region of chromosome 13 and contained no centromeric alpha-satellite DNA. The marker chromosome was not found in blood from the parents. This case represents a novel symmetrical structure with a previously unreported neocentromere locus, leading to an unusual phenotype. Similar cases of individuals with a chromosome 13 with a neocentromere have been reported. They are reviewed and compared with the current case. The importance of scanning metaphases for abnormalities in individuals presenting with asymmetry is emphasized.

Molecular cytogenetic identification and characterization of a de novo supernumerary neocentromeric derivative chromosome 13

“…Despite the fact that the cases of Tohma et al (1998) and Barwell et al (2004) show also a neocentromere location in 13q31, the euchromatic content of their derivative 13q is much smaller (13q31 K qter) in comparison to our case (13q21.3 K qter).…”

“…However, neocentromeric sites in 3q, 13q, and 15q collectively account for approximately half of all cases reported in the literature (Amor et al, 2002;Li et al, 2002). Altogether, nine cases described in the literature are characterized by a supernumerary inverted duplicated derivative chromosome 13 refl ecting a partial tetrasomy for material of 13q (Depinet et al, 1997;Lozzio et al, 1997;Warburton et al, 1997;Tohma et al, 1998;Govaerts et al, 1999;Li et al, 2002;Barwell et al, 2004). The chromosomal inversion breakpoints are located between chromosomal bands 13q14 and 13q32; the distal border of the partial tetrasomy is 13qter in all cases.…”

“…In three cases the breakpoint is not the location of the neocentromere (Warburton et al, 1997;cases JM and BC in Li et al, 2002). In the case of Barwell et al (2004), a CENP-C staining has not been performed, but they concluded that the neocentromeric constriction was apparently at the symmetrical point within band 13q31.…”

“…Most, but not all neocentric derivative chromosomes derived from chromosome 13 are composed of an inverted duplication refl ecting a partial tetrasomy in each affected cell. To the best of our knowledge only 14 supernumerary neocentric derivative chromosomes leading to a partial imbalance of 13q have been described in the literature (Depinet et al, 1997;Lozzio et al, 1997;Warburton et al, 1997;Dowhanick et al, 1998;Tohma et al, 1998;Govaerts et al, 1999;Rivera et al, 1999;Morrissette et al, 2001;Li et al, 2002;Barwell et al, Abstract. We report a young girl with microphthalmia, conductive deafness, aortic isthmus stenosis, laryngomalacia, and laryngeal stenosis carrying a de novo supernumerary neocentromeric derivative chromosome 13.…”

“…All these cases, except the case of Barwell et al (2004), are clinically and cytogenetically reviewed in Warburton et al (2000) and Amor and Choo (2002). Only nine of these cases have a supernumerary inverted duplicated derivative chromosome 13 refl ecting a partial tetrasomy for material of 13q (Depinet et al, 1997;Lozzio et al, 1997;Warburton et al, 1997;Tohma et al, 1998;Govaerts et al, 1999;Li et al, 2002;Barwell et al, 2004).…”