Interpretation of results for the molecular diagnosis of mutations in the connexin 26 gene is difficult in almost one third of cases. Close collaboration between geneticists familiar with deafness and otolaryngologists is essential to provide a high standard of genetic advice.

serological rebound is common in children with congenital toxoplasmosis but, due to the risk and constraints, an additional course of treatment and more ophthalmological surveillance than currently practiced do not seem warranted.

No abstract

The integrin-b 3 gene (ITGB3), located on human chromosome 17q21.3, was previously identified as a quantitative trait locus (QTL) for 5-HT blood levels and has been implicated as a candidate gene for autism spectrum disorder (ASD). We performed a family-based association study in 281 simplex and 12 multiplex Caucasian families. ITGB3 haplotypes are significantly associated with autism (HBAT, global P¼0.038). Haplotype H3 is largely over-transmitted to the affected offspring and doubles the risk of an ASD diagnosis (HBAT P¼0.005; odds ratio (OR)¼2.000), at the expense of haplotype H1, which is undertransmitted (HBAT P¼0.018; OR¼0.725). These two common haplotypes differ only at rs12603582 located in intron 11, which reaches a P-value of 0.072 in single-marker FBAT analyses. Interestingly, rs12603582 is strongly associated with pre-term delivery in our ASD patients (P¼0.008). On the other hand, it is SNP rs2317385, located at the 5¢ end of the gene, that significantly affects 5-HT blood levels (Mann-Whitney U-test, P¼0.001; multiple regression analysis, P¼0.010). No gene-gene interaction between ITGB3 and SLC6A4 has been detected. In conclusion, we identify a significant association between a common ITGB3 haplotype and ASD. Distinct markers, located toward the 5¢ and 3¢ ends of the gene, seemingly modulate 5-HT blood levels and autism liability, respectively. Our results also raise interest into ITGB3 influences on feto-maternal immune interactions in autism. INTRODUCTIONAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder, characterized by different levels of impairment in social interaction and communication, by stereotypies and rigid patterns of behavior, and disease onset before 3 years of age (OMIM 209850). 1 ASD is believed to primarily stem from genetic factors, based on the observation of 60-92% concordance rates in monozygotic twins vs 0-10% in dizygotic twins, with heritability estimated at or above 90%. 2,3 The cause underlying autism in the majority of patients remains unknown, although several known medical conditions account for B10% of cases. 4 ASD, similar to many other complex human disorders, does not show a simple inheritance pattern, as it may involve multiple common variants, each conveying a modest effect in epistatic interaction, rare variants with high penetrance, or perhaps more likely the coincidence of a rare variant acting upon a genetic background rendered vulnerable by a set of common variants. 2-5 Accordingly, familial aggregation of 'endophenotypes' , heritable quantitative traits distributed continuously among ASD patients and first-degree relatives, can promote the search of genetic susceptibility factors in ASD.