RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications.

The translocation t(8;16)(p11;p13) is associated with acute myeloid leukemia displaying monocytic differentiation (AML FAB M4/5) and fuses the MOZ (also named MYST3) gene (8p11) with the CBP (also named CREBBP) gene (16p13). Detection of the chimeric RNA fusions has proven difficult; only three studies have described successful amplification of the chimeric MOZ-CBP and CBP-MOZ fusions by reverse transcriptase-polymerase chain reaction (RT-PCR). We analyzed four cases of AML M4/5 with t(8;16)(p11;p13) by RT-PCR and fluorescence in situ hybridization (FISH) and characterized the reciprocal RNA fusions from three cases. We cloned both genomic translocation breakpoints from one case by long-range PCR and successfully applied RT-PCR to monitor minimal residual disease (MRD) between clinical complete remission and relapse. In three cases, the genomic breakpoints occurred in MOZ intron 16 and CBP intron 2. In one case, no fusion transcript was detected. The available data suggest clustering of t(8;16)(p11;p13) breakpoints in these introns leading to reciprocal in-frame MOZ exon 16/CBP exon 3 and in-frame CBP exon 2/MOZ exon 17 chimeric transcripts in the majority of cases. The described RT-PCR strategy may be valuable both for the routine detection of the t(8;16)(p11;p13) as well as for monitoring of MRD in this prognostically unfavorable patient group.

Clinical and molecular cytogenetic characterization of two patients with partial trisomy 1q41-qter: further delineation of partial trisomy 1q syndrome.

We report the clinical and molecular cytogenetic characterization of two patients with partial trisomy 1q. The first patient is a currently 11-year-old female proposita with a de novo unbalanced translocation 46,XX,der(8)(8qter-8p23.3::1q41-1qter), leading to a partial trisomy 1q41-qter and a partial monosomy for 8p23.3-pter. The most prominent clinical features of the girl are a triangular face, almond-shaped eyes, low-set ears, short stature with relatively long legs, and mild psychomotor retardation. To our knowledge, the cytogenetic aberration in this girl is the most proximal partial trisomy 1q leading to a mild phenotype. Recently, we identified a second patient with a similar partial trisomy 1q combined with a cri du chat syndrome caused by a de novo unbalanced translocation 46,XX,der(5)(5qter-5p13.1::1q41-1qter). Comparison of the phenotype of the two girls as well as with already published trisomy 1q cases was performed, and fluorescence in situ hybridization probes from selected YACs were used to delineate the extent of the partial trisomy in more detail.

Candidate region for Gilles de la Tourette syndrome at 7q31.

Gilles de la Tourette Syndrome (GTS) is a complex neuropsychiatric disorder characterized by motor and vocal tics. The cause of this syndrome is unknown, although based on family studies there is evidence of a strong genetic component. We report on a 13-year-old boy with GTS, minor physical anomalies, and a de novo partial duplication of chromosome 7q [dup(7)(q22.1-q31.1)]. The distal breakpoint in our patient is similar to the breakpoint of an apparently balanced familial translocation t(7;18) segregating with GTS. Together, these cases provide evidence that a gene located in the breakpoint region at 7q31 can be involved in the formation of GTS.

Chronic myeloid leukemia with a rare variant Philadelphia translocation: t(9;10;22)(q34;q22;q11).

We report a 59-year-old, male, chronic myeloid leukemia patient with a rare variant Philadelphia (Ph) translocation t(9;10;22)(q34;q22;q11). Fluorescence in situ hybridization with whole chromosome paints was used to confirm the cytogenetic findings. With a BCR/ABL-specific probe, the known rearrangement on the derivative chromosome 22 was found. The prognostic implications as well as the relevance of the additional breakpoint region 10q22 are discussed.

[Cerebrotendinous xanthomatosis. Hereditary lipid storage disease leading to bilateral swelling of Achilles tendon]. / Zerebrotendinöse Xanthomatose. Bilaterale Achillessehnenschwellung durch angeborene Stoffwechselstörung.

Cerebrotendinous xanthomatosis is a rare hereditary lipid storage disease characterised by deposits of cholestanol. In a female patient with bilateral swelling of the Achilles tendon who underwent biopsy, cerebrotendinous xanthomatosis was confirmed by combining disease patterns. She suffered from ataxia, depression, epilepsy, reduced intelligence, bilateral cataracts, gallstones, and atherosclerosis. Concentration of serum cholestanol was 10 times higher than normal. As causal therapy, ursodeoxycholic acid and statin drugs were prescribed to halt progression.