Aicardi syndrome associated with autosomal genomic imbalance: coincidence or evidence for autosomal inheritance with sex-limited expression?

Aicardi syndrome (AIS), a rare neurodevelopmental disorder thought to be caused by an X-linked dominant mutation, is characterized by 3 main features: agenesis of corpus callosum, infantile spams and chorioretinal lacunae. A genome-wide study of a girl with AIS lead us to identify a 6q deletion;12q duplication, derived from a maternal 6q;12q translocation. The two intellectually impaired brothers of the proband showed the same genomic anomalies, but not the constellation of features characterizing the AIS. This could be either a coincidental observation of 2 rare conditions, but can also suggest an alternative hypothesis for the genetic etiology of AIS, indicating the existence of a subset of autosomal genes whose mutation could act in a sex-confined manner.

Prenatal diagnosis and molecular characterization of an interstitial 1q24.3-31.3 deletion: case report and review.

We describe a foetus with an interstitial deletion of 1q detected in amniotic fluid cells and we review the literature of similar pre- and postnatal cases, in order to identify prognostic factors useful for prenatal counselling. Foetal/parents karyotyping and FISH with whole chromosome 1 paint and BAC clone specific for 1q23-32 region were performed. Further 100 Kb resolution array-CGH analysis was executed after pregnancy termination on DNA extracted from foetal skin fibroblasts. Cytogenetic analyses revealed a de novo interstitial deletion involving the long arm of chromosome 1. FISH analysis confirmed that the deletion involves the intermediate 1q31.2 region. Foetal ultrasound (US), performed at 21 weeks of gestation, showed intrauterine growth restriction, shortening of the long bones, echogenic intracardiac focus and mild cerebral ventriculomegaly. Array-CGH localized the deletion in a DNA sequence of about 21 Mb in the 1q24.3-q31.3 region. Our findings, together with available data on patients with 1q deletion, suggest that the most severe phenotypes are not simply associated with larger deletion, and that the results of prenatal US assessment, rather than a fine molecular characterization of the deletion, should be taken into account for prognostic evaluation.

MASA syndrome: ultrasonographic evidence in a male fetus.

The recent identification of a common etiology among MASA syndrome (McKusick 303300), X-linked hydrocephalus (HSAS) (McKusick 307000) and other related neurological disorders, which had previously been considered distinct nosological entities, allowed us to diagnose MASA syndrome in a male fetus in a primigravida at the 29th week of gestation by sonographic signs of the MASA spectrum such as hydrocephalus and hypoplasia of corpus callosum. Indeed, the evidence of an X-linked neurological disease in the brother and the maternal uncle of the pregnant women enabled us to estimate a 25% risk of a male fetus being an affected hemizygote. The way in which a prenatal diagnosis, based on instrumental procedures, was reached is described since the authors were unable to perform, at the time of the observation, a molecular confirmation which was carried out only after birth.

Expression of aphidicolin-induced fragile sites in lymphocytes of patients with breast cancer.

The expression of fragile sites induced by aphidicolin (APC) was evaluated on metaphase chromosomes obtained from the peripheral blood lymphocytes of 26 women with breast cancer and 15 sex- and age-matched normal controls. Both the proportion of damaged cells (P < 0.001) and the mean number of gaps and breaks per cell (0.02 < P < 0.05) were significantly higher in the patient group. There were no differences in either the age-related fragile site levels or the expression of single fragile sites between patients and controls. Our findings indicate an increased genetic instability in women with breast carcinoma.

Interleukin-1 alpha: regulation of cellular proliferation and collagen synthesis in cultured human osteoblast-like cells.

In this work the authors studied the effects of interleukin-1 alpha on metabolic activities of human osteoblast-like cells in vitro. The bone nature of the cells was established by assaying for specific bone protein, the osteonectin, and the parathormone receptor, an osteoblast marker. Administration of interleukin-1 alpha to cultured osteoblasts produce an increase in cellular proliferation as suggested by 3H-thymidine incorporation and cell growth studies. Interleukin-1 alpha also affected collagen synthesis confirming its potential role on bone-formation and resorption processes.

Trisomy 4 in acute nonlymphocytic leukemia. Report of two cases and review of the literature.

Two patients with M2 subtype of acute nonlymphocytic leukemia (ANLL) and trisomy 4 as a primary karyotype change are described. The abnormality was observed in 100% of bone marrow (BM) metaphases in both cases. It appeared alone in one case and was associated with trisomy 13 in 94% of metaphases in the other. These are the second and third cases of ANLL with trisomy 4 documented in Italy. Neither patient appears to have incurred any environmental or therapeutic insult.