Cri du chat mosaicism: an unusual case of partial deletion and partial deletion/ duplication of the short arm of chromosome 5, leading to an unusual cri du chat phenotype.

The Cri du Chat Syndrome (CdCS) is one of the most common deletion syndromes, involving the short arm of chromosome 5, with an incidence of 1 in 50.000 live births. The following are the characteristic features of this syndrome: microcephaly, hypertelorism, round face, micrognatia, epicanthic folds, prominent nasal bridge, hypotonia and severe psychomotor retardation. Patients also show a high pitched cry similar to the mewing of a cat. Deletions and duplications of chromosome 5p have been described in the literature. Mosaicism represents only 3% of this cytogenetic aberration. Up to date, only cases of de novo 5p mosaic anomalies involving two or three rearranged cell lines, with deletions and duplications, have been described. Herein, we report the first case of a patient affected by multiple congenital anomalies and a mosaicism, with two rearranged cell lines: one with a 5p deletion; the other with a 5p deletion/duplication. Our patient did not show the characteristic features described in patients with 5p duplications, but a phenotype compatible with the CdCS. Our case represents the first description of a mosaicism with deletion and deletion/duplication of a portion of the short arm of chromosome 5.

Frequency of the thiopurine S-methyltransferase alleles in the ancient genetic population isolate of Sardinia.

BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an enzyme involved in the normal metabolic inactivation of thiopurine drugs. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it was shown that inter-individual differences in response to these drugs is largely determined by genetic variation at the TPMT locus. OBJECTIVE: This study was designed to investigate in the Sardinian population the frequency distribution of four of the most common variants accounting for TPMT deficiency and to conduct comparative analyses with other populations in order to obtain insights into the main factors that have shaped diversity at the TPMT locus in Sardinia. METHODS: DNA was extracted in 259 Sardinians and the frequencies of allelic variants of TPMT were determined using polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: Among the 259 Sardinians genotyped, 6.95% were found to be heterozygous for one of four TPMT variants screened; for each variant the frequency estimate was 1.74%, 0.58%, 0.39% and 0.77% for TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C respectively. CONCLUSIONS: Although Sardinia does not show reduced diversity at the TPMT locus, the spectrum of TPMT allele frequencies affords evidence of remarkable influence of genetic drift and founder effects throughout its population history. In the broad context of the European TPMT diversity, the Sardinians come out as outliers, an observation consistent with previous genetic inferences that Sardinia has features of a genetic isolate.

Acute lymphoblastic leukemia in a child with constitutional ring chromosome 21.

This report describes a case of acute lymphoblastic leukemia with non-B, non-T, common acute lymphocytic leukemia antigen-positive blasts in a 13-year-old child with constitutional ring chromosome #21. Because ring chromosome #21 is a rare chromosomal disorder, it is likely that the leukemia transformation is related to the chromosomal anomaly.