title: The phenotype of persons having mosaicism for trisomy 21/Down syndrome reflects the percentage of trisomic cells present in different tissues.
abstract: 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.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298-0662, USA.
authors.forename: Paulie
authors.initials: P
authors.lastname: Papavassiliou
authors.forename: Timothy P
authors.initials: TP
authors.lastname: York
authors.forename: Nurcan
authors.initials: N
authors.lastname: Gursoy
authors.forename: Gloria
authors.initials: G
authors.lastname: Hill
authors.forename: Lauren Vanner
authors.initials: LV
authors.lastname: Nicely
authors.forename: Usha
authors.initials: U
authors.lastname: Sundaram
authors.forename: Allison
authors.initials: A
authors.lastname: McClain
authors.forename: Steven H
authors.initials: SH
authors.lastname: Aggen
authors.forename: Lindon
authors.initials: L
authors.lastname: Eaves
authors.forename: Brien
authors.initials: B
authors.lastname: Riley
authors.forename: Colleen
authors.initials: C
authors.lastname: Jackson-Cook
mesh_terms: D000293:Adolescent; D000328:Adult; D002467:Cell Nucleus / Q000235:genetics; D002610:Cheek; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000145:classification / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D009030:Mosaicism; D009061:Mouth Mucosa / Q000648:ultrastructure; D009928:Organ Specificity; D010641:Phenotype; D055815:Young Adult