Mosaic tetrasomy 5p resulting from an isochromosome 5p marker chromosome: case report and review of literature

We report on the fifth case, and oldest reported patient, of an individual affected with mosaic tetrasomy 5p resulting from an isochromosome 5p [i(5)(p10)] marker chromosome. A syndrome of mosaic tetrasomy 5p is defined, and includes the following features seen in the reported cases: developmental delay, seizures, ventriculomegaly (other brain anomalies), small stature/growth delay and mosaic pigmentary skin changes. Other findings include various dysmorphic facial features as well as hand and foot anomalies. This syndrome is likely more common than suggested in the literature, as the clinical presentation can be variable, and the chromosome anomaly is unlikely to be found on routine karyotype of peripheral blood lymphocytes. The i(5)(p10) marker chromosome is found only as a mosaic anomaly, with levels ranging from 0% to 10% in cultured lymphocytes to 12-85% in cultured skin fibroblasts. Microarray analysis performed on unstimulated lymphocytes from the patient in this report did not detect any evidence of the chromosome abnormality, indicating that this methodology may not be useful as a diagnostic tool in this disorder. Diagnosis of the mosaic tetrasomy 5p syndrome will rely on good clinical assessment, and appropriate cytogenetic studies, including analysis of skin fibroblasts. A child with unexplained developmental delay, seizures, hypotonia, and ventriculomegaly with or without dysmorphic features should be assessed carefully for pigmentary changes of the skin. If a diagnosis of mosaic 5p tetrasomy is suspected, karyotype of cultured fibroblasts in addition to routine cytogenetic analysis, to look for this marker chromosome is warranted.     

Proximal 5p trisomy resulting from a marker chromosome implicates band 5p13 in 5p trisomy syndrome

We describe an infant with trisomy of (5)(p10p13.1) resulting from a de novo marker chromosome. The marker's origin was identified by chromosome microdissection and reverse in situ hybridization. The clinical findings are compared to those of other partial and complete 5p duplications. This case further defines the critical region of 5p trisomy syndrome to proximal 5p. Am. J. Med. Genet. 87: 6–11, 1999. © 1999 Wiley-Liss, Inc.     

Gain of an isochromosome 5p: a new recurrent chromosome abnormality in acute monoblastic leukemia.

In acute myeloid leukemia (AML) close associations are known between cytomorphology and cytogenetics such as in AML M3/M3v showing a t(15;17) and in AML M4eo associated with inv(16)/t(16;16). In AML M5 a heterogenous cytogenetic pattern is observed. We describe the gain of an isochromosome of the short arm of chromosome 5 together with the gain of chromosome 8 as the sole abnormalities in two cases of acute monoblastic leukemia. In a third case of acute monoblastic leukemia we also observed the gain of an isochromosome 5p together with trisomy 8. This patient showed in addition an unbalanced translocation between the long arm of chromosome 1 and the short arm of chromosome 14 leading to a trisomy 1q. So far only two cases of AML with i(5)(p10) have been published. In no other hematological malignancy has an isochromosome 5p been reported up to now. As an isochromosome 5p can be misinterpreted as a deletion 5q, which occurs frequently in AML, fluorescence in situ hybridization with loci specific probes is a helpful method to detect this rare abnormality.     

Mosaic isochromosome 8p

Findings in a patient with mosaic isochromosome 8p are compared with those of previously reported cases. There were no distinguishing findings on physical examination; all had cognitive delays, especially in speech and language development. © 1993 Wiley-Liss, Inc.     

Molecular identification of a small supernumerary marker chromosome by in situ hybridization: diagnosis of an isochromosome 18p with probe L1.84

A dysmorphic child was found by cytogenetic analysis to have an extra small marker chromosome. The marker chromosome was shown to possess a chromosome 18 centromere by in situ hybridization, and probably represents an isochromosome 18p. Centromere specific probes should be of value in identifying extra small marker chromosomes, and thereby provide better understanding of the clinical significance of these.     

Pure trisomy 10p involving an isochromosome 10p

We report a child with trisomy 10p due to a translocation of the long arm of chromosome 10 to the short arm of chromosome 14 and isochromosome formation of 10p [46,XX,i(10)(p10),der(14)t(10;14)(q10;p10)]. Most reported cases of trisomy 10p involve double segmental imbalance. In contrast, the clinical features described in the current case represent pure trisomy 10p and, thus, delineate the 10p trisomy syndrome phenotype. Mechanisms of the chromosomal rearrangements in this case are suggested.     

De novo isochromosome 18p in two patients: cytogenetic diagnosis and confirmation by chromosome painting

This report concerns two patients with clinical features typical for tetrasomy 18p syndrome. Chromosomal analysis revealed a male karotype in both cases, with an additional small metacentric marker chromosome, putatively an i(18p). Fluorescent in situ hybridization with a chromosome 18-specific paint confirmed that the marker chromosome consisted of chromosome 18 material in both cases.     

Complete trisomy 5p owing to de novo translocation t(5;22)(q11;p11) with isochromosome 5p associated with a familial pericentric inversion of chromosome 2, inv 2(p21q11).

A boy with a de novo translocation (5;22) and isochromosome 5p associated with a pericentric inversion of chromosome 2 (p21q11) is described. The pericentric inversion was also present in the mother. The main clinical features of the 'complete trisomy 5p' syndrome were present in the proband.     

Maternal isochromosome 7q and paternal isochromosome 7p in a boy with growth retardation

A 12-year 9-month-old boy with postnatal growth retardation, normal psychomotor development, and minor anomalies that included a triangular-shaped face, small nose, and narrow and high-arched palate is reported. The constitutional karyotype was 46,XY,i(7)(p10),i(7)(q10). Molecular investigations revealed the presence of a maternal isodisomy 7q and a paternal isodisomy 7p. The clinical and molecular findings are notably congruent with a recently reported case and support the hypothesis of one or more maternally imprinted genes located on the long arm of chromosomes 7 that regulate, in particular, postnatal growth.     

Double supernumerary isochromosome 9p in myeloproliferative syndrome

The presence of supernumerary isochromosome 9p in duplicate in about 50% of bone marrow cells of an elderly female patient with myeloproliferative syndrome is reported.     

19p + marker chromosome correlates with relapse in malignant fibrous histiocytoma

In this study, we examined the relationship of 19p13 aberrations, usually leading to addition of unknown material (19p +), and ring chromosomes to clinical outcome in patients with malignant fibrous histiocytoma (MFH). Analysis of 69 MFHs revealed 19 tumors with 19p + and 24 tumors with ring chromosomes. After a median follow-up period of 36 months, 24 patients developed metastases, and 27 patients developed local recurrences. Ten patients had both local recurrences and metastases. Local recurrence was more common in association with 19p + than without. Metastasis was more common with 19p + tumors in high-risk patients (tumor size > 5 cm and grade III–IV; n = 48) than those without 19p +. There was a trend suggesting fewer relapses after tumors with ring chromosomes. 19p + may be an independent marker of unfavorable outcome in MFH. Genes Chromosom Cancer 16:88–93 (1996). © 1996 Wiley-Liss, Inc.     

A new case of "complete" trisomy 5p with isochromosome 5p associated with a de novo translocation t(5;8)(q11;p23)

A boy with a de novo translocation t(5;8)(q11;p23) and an isochromosome 5p is described. The main clinical features found in the complete trisomies 5p are reviewed and the mechanisms of the chromosomal rearrangements involving centromeric and telomeric regions are discussed.     

The human dendritic cell marker CD83 maps to chromosome 6p23

The chromosomal localization of the human CD83 gene was determined using somatic cell hybrids, a radiation hybrid mapping panel and FISH analysis on human metaphase chromosomes. PCR-based analysis of a single chromosome hybrid panel identified the presence of the CD83 gene on human chromosome 6 and subsequent analysis of the Genebridge4 radiation panel located the gene between AFMa192wg9 and AFMb322wd1 with a lod score of 9.2. Finally, using FISH analysis the CD83 gene was localized to chromosome 6 band p23.     

Trisomy 7p resulting from isochromosome formation and whole-arm translocation

A newborn boy with a large anterior fontanel, minor facial anomalies, postaxial polydactyly, patent ductus arteriosus, and developmental delay had trisomy of 7p due to an i(7p) and a concomitant t(2;7) (q37.3; q11.1). Significant enlargement of the fontanel is the most characteristic finding in most patients with duplications involving 7p15-pter. Asynchrony in fore- and hindbrain and hemisphere formation leading to brain asymmetry and various defects in the posterior fossa are typical of infants with duplications of 7p11-p12. A variety of heart defects has also been found in more than 50% of patients with duplication of 7p segments. Isochromosome formation accompanied by whole-arm translocation, resulting in uniparental isodisomy for the involved segment, is an extremely rare cause leading to partial trisomies. Although it is not clear whether isochromosome formation precedes the whole-arm translocation or follows it, the secondary rearrangement may have adaptive significance. © 1995 Wiley-Liss, Inc.     

Prezygotic origin of the isochromosome 12p in Pallister-Killian syndrome

Pallister-Killian syndrome is a rare disorder comprising multiple congenital anomalies, streaks of hypo(hyper)pigmentation, seizures, profound mental retardation, and the presence of an extra metacentric chromosome i(12)(p10), usually limited to skin fibroblasts. The mechanism and parental origin of the extra chromosome i(12)(p10) are unknown. Here, we present a girl with Pallister-Killian syndrome and the i(12)(p10) in 50% of cultured skin fibroblasts. Using micro-satellite DNA markers of chromosome 12p, we detected 3 alleles—including 2 different alleles of maternal origin—in cultured skin fibroblasts, suggesting that the tetrasomy 12p is the result of a prezygotic event, with a nondisjunction event during maternal meiosis. Am. J. Med. Genet. 69:166–168, 1997. © 1997 Wiley-Liss, Inc.