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.

[Correlation between major histocompatibility complex (MHC)-class II and type 1 diabetes]. / Correlazione fra MHC di classe II e diabete mellito di tipo 1.

The autoimmune disease type 1 diabetes (T1D) results from a T lymphocyte-dependent, selective destruction of the insulin-producing pancreatic beta-cells and subsequent irreversible insulin deficiency. The disease is caused by a combination of genetic and environmental factors. Numerous genetic, structural and biological studies have provided a convincing case that in human T1D and in its murine model, the non obese diabetes (NOD) mouse, the major histocompatibility complex (MHC) class II molecules, HLA-DQB1 and -DRB1 and their murine orthologues, IA and IE, are the major genetic determinants. The two loci act as a complex superlocus, with both haplotype- and genotype-specific effects. In humans the HLA class II molecule-association with the disease is constituted by a two-sided gradient from positively associated-high risk to negatively associated-low risk molecules. Very low risk corresponds to dominant protection from the disease. The protein structure of DQ/IA and DR/IE molecules have been established. Molecular modeling work revealed that there are marked similarities both within, and cross species between T1D protective class II molecules. Likewise, the T1D predisposing molecules show conserved similarities that differ with the shared structural patterns observed between the protective molecules. The available data provide evidence for a joint action of the class II peptide-binding pockets P1, P4 and P9 in disease susceptibility and resistance with a main role for P9 in DQ/IA and for P1 and P4 in DR/IE. Overall these observations suggest shared pathways in human and murine T1D.