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The ability to accurately predict the likelihood of expansion of the CGG repeats in the FMR1 gene to a full mutation is of critical importance for genetic counseling of women who are carriers of premutation alleles (55–200 CGG repeats) and who are weighing the risk of having a child with fragile X syndrome. The presence of AGG interruptions within the CGG repeat tract is thought to decrease the likelihood of expansion to a full mutation during transmission, thereby reducing risk, although their contribution has not been quantified. We retrospectively analyzed 267 premutation alleles for number and position of AGG interruptions, length of pure CGG repeats, and CGG repeat lengths present in the offspring of the maternal transmissions. In addition, we determined the haplotypes of four markers flanking the 5′-UTR locus in the premutation mothers. We found that the presence of AGG interruptions significantly increased genetic stability, whereas specific haplotypes had a marginal association with transmission instability. The presence of AGG interruptions reduced the risk of transmission of a full mutation for all maternal (premutation) repeat lengths below ~100 CGG repeats, with a differential risk (0 vs. 2 AGG) exceeding 60% for alleles in the 70- to 80-CGG repeat range. Genet Med 2012:14(8):729–736

Background Autism spectrum disorders (ASD) are neurodevelopmental disorders of complex etiology, with a recognized substantial contribution of heterogeneous genetic factors; one of the core features of ASD is a lack of affiliative behaviors. Methods On the basis of the existing literature, in this study we examined the hypothesis of allelic associations between genetic variants in six genes involved in control of maternal and affiliative behaviors ( OXT, OXTR, PRL, PRLR , D β H , and FOSB ). One hundred and seventy-seven probands with ASD from 151 families ( n = 527) were assessed with a set of related instruments capturing multiple facets of ASD. Multivariate and univariate phenotypes were constructed from these assessments and subjected to genetic linkage and association analyses with PBAT and FBAT software. Results The resulting pattern of findings, in general, confirmed the hypotheses of the significance of the genes involved in the development of affiliative behaviors in the manifestation of ASD ( p values ranging from .000005 to .05); statistically speaking, the strongest results were obtained for allelic associations with the PRL, PRLR , and OXTR genes. Conclusions These preliminary data provide additional support for the hypothesis that the allelic variants of genes necessary for the development of species-typical affiliative behaviors are associated with ASD. Independent replication of these findings is needed and studies of other genes associated with affiliative behaviors are indicated.