Low‐level mosaicism of trisomy 14: Phenotypic and molecular characterization

Abstract

Trisomy 14 mosaicism is a rare cytogenetic abnormality with a defined and recognizable clinical phenotype. We present a detailed clinical history and physical findings of five patients with low-level mosaicism of trisomy 14 detected by array-based comparative genomic hybridization (array-CGH) analysis or by routine chromosome analysis. These patients exhibited growth and developmental delays with variable severity, congenital anomalies, pigmentary skin lesions, and dysmorphic features. The phenotype of our patients was compared with previously described cases. This report suggests that trisomy 14 mosaicism may be more common than has been previously appreciated and also illustrates the important application of array-CGH to detect low-level mosaic chromosome abnormalities. We predict that a wider application of the array-CGH technology will significantly increase the detection rate of low-level mosaicism and will subsequently improve our ability to provide a diagnosis for patients with dysmorphic features, congenital anomalies, and developmental delay.

Detection of low-level mosaicism and placental mosaicism by oligonucleotide array comparative genomic hybridization

“…aCGH will likely become an invaluable tool for the detection of clinically relevant mosaic abnormalities as evidenced by the recent identification of postnatal mosaic tetrasomy 12p 39 and trisomy 14, 40 and prenatal mosaic trisomy 8q. 41 In addition, our finding of previously unidentified placental mosaicism in POC specimens with double trisomies using oligonucleotide aCGH underscores the importance of careful interpretation when performing aCGH on DNA from uncultured direct specimens.…”

Partial and complete trisomy 14 mosaicism: clinical follow-up, cytogenetic and molecular analysis

“…Trisomy 14 mosaicism is a rare chromosomal abnormality with an incidence of 3:1 females compared to males and is associated with multiple congenital anomalies [1-3]. The most common clinical characteristics (Table 1) are growth and psychomotor retardation, dysmorphic craniofacial features such as broad nose, abnormal or low-set ears, micrognathia, cleft or highly arched palate, short neck, congenital heart and genitourinary abnormalities [3,4].…”

“…The most common clinical characteristics (Table 1) are growth and psychomotor retardation, dysmorphic craniofacial features such as broad nose, abnormal or low-set ears, micrognathia, cleft or highly arched palate, short neck, congenital heart and genitourinary abnormalities [3,4]. Other features reported are hypertelorism, body asymmetry and abnormal skin pigmentation [1,2].…”

Low-frequency Mosaicism of Trisomy 14, Missed by Array CGH

“…19) Several reports reveal that G-banded karyotyping may underestimate the level of aneuploidy. 3,4,19) Although estimated mosaicism proportion (18.0%) by array CGH was lower than by karyotyping (23.3%) in this study, direct comparison between percent aneuploidy by karyotype using cultured cells and by array CGH using uncultured cell should be interpreted cautiously. Because we only detected counted aneuploidy 14 on PHAstimulated cultured T-cells.…”

“…Chromosomal mosaicism has been implicated as a leading genetic cause of human prenatal death, early prenatal brain development, congenital malformations, and many human diseases. [1][2][3] Several renowned mosaic chromosome syndromes include genetic disease such as Pallister-Killian syndrome (tetrasomy 12p mosaicism [PKS, OMIM 601803]), Hypermelanosis of Ito (HMI, OMIM 300337) and milder versions of known diseases (e.g., mosaic Down syndrome and mosaic Klinefelter syndrome). 4) Mosaic trisomy 14 syndrome is a well-known but unusual chromosomal abnormality with a distinct and recognizable phenotype.…”