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The phenotype of persons having mosaicism for trisomy 21/Down syndrome reflects the percentage of trisomic cells present in different tissues
Author(s) -
Papavassiliou Paulie,
York Timothy P.,
Gursoy Nurcan,
Hill Gloria,
Nicely Lauren Vanner,
Sundaram Usha,
McClain Allison,
Aggen Steven H.,
Eaves Lindon,
Riley Brien,
JacksonCook Colleen
Publication year - 2009
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32729
Subject(s) - trisomy , buccal swab , phenotype , buccal mucosa , biology , down syndrome , aneuploidy , karyotype , buccal administration , lymphocyte , pathology , genetics , andrology , immunology , chromosome , gene , medicine , bioinformatics , oral cavity , orthodontics
Little is known about the pathogenesis of the phenotype in individuals with trisomy 21 mosaicism and Down syndrome. The primary goal of this study was to identify factors contributing to the observed phenotypic variation by evaluating 107 individuals having trisomy 21 mosaicism. To investigate a potential “threshold” effect due to trisomic imbalance, lymphocyte and buccal mucosa nuclei were scored using FISH. Overall, buccal cells showed a significantly higher frequency of trisomy than lymphocytes ( P < 0.0001). Using latent class analysis, two phenotypic classes were identified based on the clinical findings of the propositi. Patients from class 1 had significantly fewer traits and a lower percentage of trisomic cells (mean of 37.3% lymphocytes; 34.5% buccal mucosa cells) when compared to those stratified into class 2 (54.0% lymphocytes; 53.4% buccal mucosa cells). Tissue‐specific influences were also detected, with buccal mucosa trisomy levels being significantly correlated with IQ ( P = 0.0094; both ectodermal derivatives), while congenital heart defects were significantly correlated with lymphocytes ( P = 0.0286; both mesodermal embryonic derivatives). In conclusion, allowing for the distinction of two groups, we observed variation in phenotype, associated with the percentage of trisomic cells. We also observed tissue‐specific effects on phenotype. The results of this study should enable geneticists and other health care professionals to provide information regarding optimal diagnostic approaches and anticipated clinical outcomes. © 2009 Wiley‐Liss, Inc.