Intrachromosomal triplication 12p11.22–p12.3 and gonadal mosaicism of partial tetrasomy 12p^,**

Abstract

Cases of tetrasomy 12p and trisomy 12p are known to be associated with specific phenotypic abnormalities well described in the literature. Here, we report on the unusual case of a partial tetrasomy 12p found in an affected patient and in a mosaic constellation in the patient's mother, who showed no phenotypic abnormality. The index patient was a 16-year-old boy with clinical features similar to the "trisomy 12p syndrome" including mental retardation, macrocephaly, a short nose with anteverted nostrils, and a broad protruding lower lip. G-banding analysis and fluorescence in situ hybridization (FISH) experiments using locus specific YAC DNA probes revealed a derivative chromosome 12 with a partial triplication of the short arm with an inverted copy, flanked by two direct copies. Chromosome analyses in parental lymphocytes showed a chromosomal mosaicism in the phenotypically normal mother, with 12% cells exhibiting the same partial tetrasomy 12p as detected in her son. The allelic pattern of short tandem repeats (STR) in the mother's blood DNA showed that a chimerism can be excluded with high probability. To our knowledge, this is the first report of intrachromosomal triplication on chromosome 12, as well as partial tetrasomy 12p mosaicism. Moreover, as a consequence of the chromosomal aberration in the son it can be concluded that a gonadal mosaicism is present in the mother.

Mosaic Intrachromosomal Triplication of (12)(p11.2p13) in a Patient with Pallister-Killian Syndrome

“…Intrachromosomal triplications are rare events and the middle segment usually being inverted in orientation, as in our case [8]. In the majority of cases, triplications were interstitial, whereas there is only one published report of triplication of a whole chromosome arm [9].…”

“…In the article by Eckel et al [8], the 12p11.22-p12.3 region was triplicated and this region does not cover the critical PKS region, which defined the chromosomal region 12pter-p12.3. Therefore, the patient’s clinical phenotype was similar to trisomy 12p syndrome rather than the PKS.…”

“…Intrachromosomal triplications leading to partial tetrasomies of the certain chromosome 12 regions have been reported in two patients [8,9]. In this report, we present the third patient who has mosaic intrachromosomal triplication on the short arm of chromosome 12.…”

Persistent Mosaicism for 12p Duplication/Triplication Chromosome Structural Abnormality in Peripheral Blood

“…Two cases with triplications for all of 12p showed tissue limited mosaicism, with the abnormal cell line being present in only skin fibroblasts [7, 8]. However, two cases with triplication of 12p regions that did not include 12p13.31 were present in all tissues, including peripheral blood [9, 10]. Our patient has four copies of the region proposed to be responsible for the PKS phenotype, 12p13.31, which contains three genes, ING4, CHD4, and MAGP2, responsible for negative growth regulation [4].…”

17p11.2p12 triplication and del(17)q11.2q12 in a severely affected child with dup(17)p11.2p12 syndrome

“…We also report here for the first time a patient with tetrasomy 17p11.2p12. Triplications or partial tetrasomies for other chromosomal regions have been reported (Table 4) (48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62). Constitutional triplications of genomic regions have been associated with various disorders that include mental retardation syndromes, Pelizaeus-Merzbacher syndrome, Parkinsonism and recently, hereditary pancreatitis (63)(64)(65)(66).…”