Tetrasomy 15q25?qter: Cytogenetic and molecular characterization of an analphoid supernumerary marker chromosome

Abstract

Tetrasomy for the distal long arm of chromosome 15 is a rare finding. It has been previously described in seven patients, all of whom had a supernumerary marker chromosome (SMC) derived from distal 15q. These SMC contained no apparent centromeres (C-band/alpha-satellite negative), and belong to a novel class of SMC with neocentromeres. We present the oldest surviving patient with tetrasomy for distal 15q. The proposita was a 10-year-old girl with moderate to severe mental retardation, absent speech, hypotonia, minor facial anomalies, unusual digits, and pigmentation anomalies. Mosaicism for a symmetrical SMC was identified in metaphases from lymphocytes and fibroblasts. Parental karyotypes were normal, indicating a de novo origin for the SMC. FISH with a whole chromosome paint for chromosome 15 showed that the SMC was derived entirely from chromosome 15. However, C-banding and FISH with chromosome 15 probes D15Z1, D15S11, SNRPN, and PML were all negative. FISH with the FES probe at 15q26 showed hybridization to both ends of the SMC. The marker was interpreted as an analphoid inverted duplication of 15q25-->qter containing a presumed neocentromere. Previous molecular studies suggested either a mitotic or paternal meiotic origin for these distal 15q SMC. However, molecular analysis with chromosome 15 polymorphic markers showed that the analphoid SMC(15) in the proposita originated from a maternal meiotic error. The origins and mechanisms involved in formation of these distal 15q SMC appear to be more diverse than for the proximal pseudodicentic SMC(15).

Overgrowth and trisomy 15q26.1-qter including the IGF1 receptor gene: report of two families and review of the literature

“…We suggest that overgrowth might be causally related to a dosage excess of IGF1R gene. Interestingly, overgrowth has also been reported in patients with tetrasomy of chromosome 15q25-qter, 8 as well as in some patients with larger trisomy 15q22qter. 26,27 Mainly, this report emphasizes the importance of chromosome analysis in the investigation of patients with overgrowth and mental retardation.…”

“…7 Overgrowth has been reported as well in association with tetrasomy 15q25-qter. 8 Observations of distal deletions of chromosome 15q including the IGF1R gene suggest that growth failure might be related to IGF1R hemizygosity. 9 Here we report on four patients with overgrowth and trisomy 15q26.1-qter including the IGF1R gene.…”

Partial tetrasomy 12pter-12p12.3 in a girl with Pallister-Killian syndrome: extraordinary finding of an analphoid, inverted duplicated marker

“…Summarising the so far published data on the mechanism of formation of analphoid, inverted duplicated markers, postzygotic mitosis as cell stage of origin has been described three times, while maternal or paternal meiotic errors could each be delineated only once. 13,14 Analphoid inverted duplicated markers may be generated by a single`Utype' exchange event involving chromosome breakage and subsequent reunion between the sister chromatids. A`Utype' exchange can also be generated by a simple abnormal event in DNA replication, as suggested by Sjo Èsted et al 15 Conversely, isochromosomes of the complete chromosome 12p as well as other short arm isochromosomes mainly originate from maternal meiosis II errors followed by rearrangements leading to duplication of the short and loss of the long arm.…”

Tetrasomy 15q26: a distinct syndrome or Shprintzen-Goldberg syndrome phenocopy?

“…There have been at least 13 previously reported cases of tetrasomy 15q in the form of a marker chromosome. 10,11,15,[20][21][22][23][24][25][26][27][28][29] However, in only 10 of the 13 are specific clinical data available ( Table 1) with 9 of the 10 reported as mosaic tetrasomy 15q. Nonetheless, the craniofacial gestalt observed in all our cases is also present in eight of eight cases tetrasomic for 15q25 where clinical images are available ( Table 1).…”