We present a rare case of mosaicism for a structural abnormality of chromosome 12 in a patient with phenotypic features of Pallister-Killian syndrome. A six-month-old child with dysmorphic features, exotropia, hypotonia, and developmental delay was mosaic for both a normal karyotype and a cell line with 12p duplication/triplication in 25 percent of metaphase cells. Utilization of fluorescence in situ hybridization (FISH) identified three copies of probes from the end of the short arm of chromosome 12 (TEL(12p13) locus and the subtelomere (12p terminal)) on the structurally abnormal chromosome 12. Genome-wide SNP array analysis revealed that the regions of duplication and triplication were of maternal origin. The abnormal cell line in our patient was present at 25 percent at six months and 19 months of age in both metaphase and interphase cells from peripheral blood, where typically the isochromosome 12p is absent in the newborn. This may suggest that the gene(s) resulting in a growth disadvantage of abnormal cells in peripheral blood of patients with tetrasomy 12p may not have the same influence when present in only three copies. 1. Introduction Patients with trisomy 12p typically present with severe mental retardation, seizures, low-set ears, and characteristic facial dysmorphology including flatness of the face, small nose with broad bridge, anteverted nares, inner epicanthal folds, long philtrum, everted lower lip, and high forehead. The extra copy is due to an intrachromosomal duplication or an extra copy on a derivative chromosome. Patients with tetrasomy 12p, or Pallister-Killian syndrome (PKS), additionally present with sparse temporal hair, eyebrows, and eyelashes, prominent forehead, a cupid-bow shaped mouth, and large ears. A hallmark of PKS is tissue-limited mosaicism, with few, if any, abnormal cells found in peripheral blood lymphocyte metaphases in the newborn. Another characteristic of tetrasomy 12p is loss of the abnormal cell line in peripheral blood and skin fibroblasts as the patient ages or over time in serial-passaged cultured fibroblasts [1, 2]. We report on a patient with mosaicism for duplication and triplication of 12p. Only about 24 cases with mosaicism for a structural abnormality of an autosome have been reported in the literature [3]. Approximately 26 individuals with nonmosaic structural 12p duplications have been reported in the literature with a minimum critical region of 12p13.31 [4]. We report on a patient with mosaicism in peripheral blood for a derivative chromosome involving duplication and triplication of 12p. 2.
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