Abstract
Partial monosomy 21 was recently segregated into three regions associated with variable clinical severity. We describe 10 new patients, all examined by single nucleotide polymorphism (SNP) genotyping and G-banded karyotyping. Cohort A consisted of three patients seen in our medical genetics clinics with partial chromosome 21 monosomies. In two of these patients having terminal deletions (21q22.2-ter and 21q22.3-ter), the breakpoints differed by at least 812 Kb of sequence, containing seven RefSeq genes. A third patient had an interstitial hemizygous loss of 16.4 Mb (21q21.1–q22.11). All three patients had relatively mild phenotypes. Cohort B consisted of seven patients with partial chromosome 21 monosomies who had a greater number of dysmorphic features and some major malformations; SNP genotypes were obtained from the Coriell Genetic Cell Repository. We also collected data on partial monsomy 21 cases from the DECIPHER database. This report of 10 new cases of 21q deletion and review of a total of 36 confirms that deletion of the terminal region is associated with a mild phenotype, but suggests that deletion of regions 1 and 2 is compatible with life and have a variable phenotype perhaps relating more to other genetic and environmental variables than to genes in the interval.
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References
Lejeune J, Berger R, Rethore MO et al: Partial monosomy for a small acrocentric chromosome. C R Hebd Seances Acad Sci 1964; 259: 4187–4190.
Lyle R, Béna F, Gagos S et al: Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21. Eur J Hum Genet 2009; 17: 454–466.
Firth HV, Richards SM, Bevan AP et al: DECIPHER: database of chromosomal imbalance and phenotype in humans using ensembl resources. Am J Hum Genet 2009; 84: 524–533.
Ting JC, Roberson EDO, Miller ND et al: (2007) Visualization of uniparental inheritance, Mendelian inconsistencies, deletions, and parent of origin effects in single nucleotide polymorphism trio data with SNPtrio. Hum Mutation 2007; 28: 1225–1235.
Yao G, Chen X-N, Flores-Sarnet L et al: Deletion of chromosome 21 disturbs human brain morphogenesis. Genetics in Medicine 2006; 8: 1–7.
Keren B, Bernardin C, Toutain A et al: Pure proximal deletion of chromosome 21 and kyphosis. Eur J Med Genet 2007; 50: 469–474.
Takhar J, Malla AK, Siu V et al: An interstitial deletion of the long arm of chromosome 21 in a case of a first episode of psychosis. Acta Psychiatrica Scandinavica 2002; 106: 71–74.
Chettouh Z, Croquette M-F, Delobel B et al: Molecular mapping of 21 features associated with partial monosomy 21: involvement of the APP-SOD1 region. Am J Hum Genet 1995; 57: 62–71.
Lindstrand A, Malmgren H, Sahlén S et al: Detailed molecular and clinical characterization of three patients with 21q deletions. Clin Genet 2010; 77: 145–154.
Ehling D, Kennerknecht I, Junge A et al: Mild phenotype in two unrelated patients with a partial deletion of 21q22.2-q22.3 defined by FISH and molecular studies. Am J Med Genet Part A 2004; 131A: 265–272.
Tinkel-Vernon H, Finkernagel S, Desposito F et al: Patient with a deletion of chromosome 21q and minimal phenotype. Am J Med Genet Part A 2003; 120A: 142–143.
Acknowledgements
The authors sincerely thank the families participating in this study. We thank Nathaniel D. Miller for helpful comments on the manuscript. This work was supported in part by NIH Grant HD024061 (J.P. and GHT) and the Stem Cell Resource Center at Johns Hopkins Institute of Cell Engineering (JP).
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Roberson, E., Wohler, E., Hoover-Fong, J. et al. Genomic analysis of partial 21q monosomies with variable phenotypes. Eur J Hum Genet 19, 235–238 (2011). https://doi.org/10.1038/ejhg.2010.150
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DOI: https://doi.org/10.1038/ejhg.2010.150
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