Chromosome 13q neocentromeres

Molecular cytogenetic characterization of three additional cases and clinical spectrum

Shulan Li, Paul Malafiej, Brynn Levy, Radma Mahmood, Michael Field, Thomas Hughes, Lillian Lockhart, Zhanhe Wu, Melissa Huang, Kurt Hirschhorn, Golpalrao V N Velagaleti, Art Daniel, Peter E. Warburton

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)258-267
Number of pages10
JournalAmerican Journal of Medical Genetics
Volume110
Issue number3
DOIs
StatePublished - Jul 1 2002

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Cytogenetics
Chromosomes
Chromosomes, Human, Pair 13
Fluorescence In Situ Hybridization
Genetic Markers
Fluorescent Antibody Technique
Chromosome Painting
Satellite DNA
Chromosomes, Human, Pair 11
Comparative Genomic Hybridization
Centromere
Cytogenetic Analysis
Genetic Association Studies
Human Chromosomes
Aneuploidy
Phenotype
Antibodies
centromere protein C

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 journalArticle

Li, S, Malafiej, P, Levy, B, Mahmood, R, Field, M, Hughes, T, Lockhart, L, Wu, Z, Huang, M, Hirschhorn, K, Velagaleti, GVN, Daniel, A & Warburton, PE 2002, 'Chromosome 13q neocentromeres: Molecular cytogenetic characterization of three additional cases and clinical spectrum', American Journal of Medical Genetics, vol. 110, no. 3, pp. 258-267. https://doi.org/10.1002/ajmg.10454
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. / Chromosome 13q neocentromeres : Molecular cytogenetic characterization of three additional cases and clinical spectrum. In: American Journal of Medical Genetics. 2002 ; Vol. 110, No. 3. pp. 258-267.
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AU - Hughes, Thomas

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AU - Wu, Zhanhe

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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.

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