Abstract
We report three new cases of chromosome 13 derived marker chromosomes, found in unrelated patients with dysmorphisms and/or developmental delay. Molecular cytogenetic analysis was performed using fluorescence in situ hybridization (FISH) with chromosome-specific painting probes, alpha satellite probes, and physically mapped probes from chromosome 13q, as well as comparative genomic hybridization (CGH). This analysis demonstrated that these markers consisted of inversion duplications of distal portions of chromosome 13q that have separated from the endogenous chromosome 13 centromere and contain no detectable alpha satellite DNA. The presence of a functional neocentromere on these marker chromosomes was confirmed by immunofluorescence with antibodies to centromere protein-C (CENP-C). The cytogenetic location of a neocentromere in band 13q32 was confirmed by simultaneous FISH with physically mapped YACs from 13q32 and immunofluorescence with anti-CENP-C. The addition of these three new cases brings the total number of described inv dup 13q neocentic chromosomes to 11, representing 21% (11/52) of the current overall total of 52 described cases of human neocentric chromosomes. This higher than expected frequency suggests that chromosome 13q may have an increased propensity for neocentromere formation. The clinical spectrum of all 11 cases is presented, representing a unique collection of polysomy for different portions of chromosome 13q without aneuploidies for additional chromosomal regions. The complexity and variability of the phenotypes seen in these patients does not support a simple reductionist view of phenotype/genotype correlation with polysomy for certain chromosomal regions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 258-267 |
| Number of pages | 10 |
| Journal | American Journal of Medical Genetics |
| Volume | 110 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jul 1 2002 |
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Keywords
- Centromere
- Chromosome
- Inverted duplication
- Neocentromere
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
Chromosome 13q neocentromeres : Molecular cytogenetic characterization of three additional cases and clinical spectrum. / Li, Shulan; Malafiej, Paul; Levy, Brynn; Mahmood, Radma; Field, Michael; Hughes, Thomas; Lockhart, Lillian; Wu, Zhanhe; Huang, Melissa; Hirschhorn, Kurt; Velagaleti, Golpalrao V N; Daniel, Art; Warburton, Peter E.
In: American Journal of Medical Genetics, Vol. 110, No. 3, 01.07.2002, p. 258-267.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chromosome 13q neocentromeres
T2 - Molecular cytogenetic characterization of three additional cases and clinical spectrum
AU - Li, Shulan
AU - Malafiej, Paul
AU - Levy, Brynn
AU - Mahmood, Radma
AU - Field, Michael
AU - Hughes, Thomas
AU - Lockhart, Lillian
AU - Wu, Zhanhe
AU - Huang, Melissa
AU - Hirschhorn, Kurt
AU - Velagaleti, Golpalrao V N
AU - Daniel, Art
AU - Warburton, Peter E.
PY - 2002/7/1
Y1 - 2002/7/1
N2 - We report three new cases of chromosome 13 derived marker chromosomes, found in unrelated patients with dysmorphisms and/or developmental delay. Molecular cytogenetic analysis was performed using fluorescence in situ hybridization (FISH) with chromosome-specific painting probes, alpha satellite probes, and physically mapped probes from chromosome 13q, as well as comparative genomic hybridization (CGH). This analysis demonstrated that these markers consisted of inversion duplications of distal portions of chromosome 13q that have separated from the endogenous chromosome 13 centromere and contain no detectable alpha satellite DNA. The presence of a functional neocentromere on these marker chromosomes was confirmed by immunofluorescence with antibodies to centromere protein-C (CENP-C). The cytogenetic location of a neocentromere in band 13q32 was confirmed by simultaneous FISH with physically mapped YACs from 13q32 and immunofluorescence with anti-CENP-C. The addition of these three new cases brings the total number of described inv dup 13q neocentic chromosomes to 11, representing 21% (11/52) of the current overall total of 52 described cases of human neocentric chromosomes. This higher than expected frequency suggests that chromosome 13q may have an increased propensity for neocentromere formation. The clinical spectrum of all 11 cases is presented, representing a unique collection of polysomy for different portions of chromosome 13q without aneuploidies for additional chromosomal regions. The complexity and variability of the phenotypes seen in these patients does not support a simple reductionist view of phenotype/genotype correlation with polysomy for certain chromosomal regions.
AB - We report three new cases of chromosome 13 derived marker chromosomes, found in unrelated patients with dysmorphisms and/or developmental delay. Molecular cytogenetic analysis was performed using fluorescence in situ hybridization (FISH) with chromosome-specific painting probes, alpha satellite probes, and physically mapped probes from chromosome 13q, as well as comparative genomic hybridization (CGH). This analysis demonstrated that these markers consisted of inversion duplications of distal portions of chromosome 13q that have separated from the endogenous chromosome 13 centromere and contain no detectable alpha satellite DNA. The presence of a functional neocentromere on these marker chromosomes was confirmed by immunofluorescence with antibodies to centromere protein-C (CENP-C). The cytogenetic location of a neocentromere in band 13q32 was confirmed by simultaneous FISH with physically mapped YACs from 13q32 and immunofluorescence with anti-CENP-C. The addition of these three new cases brings the total number of described inv dup 13q neocentic chromosomes to 11, representing 21% (11/52) of the current overall total of 52 described cases of human neocentric chromosomes. This higher than expected frequency suggests that chromosome 13q may have an increased propensity for neocentromere formation. The clinical spectrum of all 11 cases is presented, representing a unique collection of polysomy for different portions of chromosome 13q without aneuploidies for additional chromosomal regions. The complexity and variability of the phenotypes seen in these patients does not support a simple reductionist view of phenotype/genotype correlation with polysomy for certain chromosomal regions.
KW - Centromere
KW - Chromosome
KW - Inverted duplication
KW - Neocentromere
UR - http://www.scopus.com/inward/record.url?scp=18444415140&partnerID=8YFLogxK
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U2 - 10.1002/ajmg.10454
DO - 10.1002/ajmg.10454
M3 - Article
VL - 110
SP - 258
EP - 267
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 3
ER -