We are performing whole genome sequencing (WGS) of families with Autism Spectrum Disorder (ASD) to build a resource, named MSSNG, to enable the sub-categorization of phenotypes and underlying genetic factors involved. Here, we report WGS of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible in a cloud platform, and through an internet portal with controlled access. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertion/deletions (indels) or copy number variations (CNVs) per ASD subject. We identified 18 new candidate ASD-risk genes such as MED13 and PHF3, and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (p=6×10−4). In 294/2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried CNV/chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.

Introduction The number of adolescents referred to specialized gender identity clinics for gender dysphoria appears to be increasing and there also appears to be a corresponding shift in the sex ratio, from one favoring natal males to one favoring natal females. Aim We conducted two quantitative studies to ascertain whether there has been a recent inversion of the sex ratio of adolescents referred for gender dysphoria. Methods The sex ratio of adolescents from two specialized gender identity clinics was examined as a function of two cohort periods (2006–2013 vs. prior years). Study 1 was conducted on patients from a clinic in Toronto, and Study 2 was conducted on patients from a clinic in Amsterdam. Results Across both clinics, the total sample size was 748. In both clinics, there was a significant change in the sex ratio of referred adolescents between the two cohort periods: between 2006 and 2013, the sex ratio favored natal females, but in the prior years, the sex ratio favored natal males. In Study 1 from Toronto, there was no corresponding change in the sex ratio of 6,592 adolescents referred for other clinical problems. Conclusions Sociological and sociocultural explanations are offered to account for this recent inversion in the sex ratio of adolescents with gender dysphoria.

This study examined whether children clinically referred for gender dysphoria (GD) show increased symptoms of autism spectrum disorder (ASD). Circumscribed preoccupations or intense interests were considered as overlapping symptoms expressed in GD and ASD. In gender-referred children (n = 534; 82.2% male) and their siblings (n = 419; 57.5% male), we examined Items 9 and 66 on the Child Behavior Checklist, which measure obsessions and compulsions, respectively. Non-GD clinic-referred (n = 1,201; 48.5% male) and nonreferred (n = 1,201; 48.5% male) children were also examined. Gender-referred children were elevated compared to all other groups for Item 9, and compared to siblings and nonreferred children for Item 66. A gender-related theme was significantly more common for gender-referred boys than male siblings on Item 9 only. A gender-related theme was not significantly more common for gender-referred girls compared to their female siblings on either item. The findings for Item 9 support the idea that children with GD show an elevation in obsessional interests. For gender-referred boys in particular, gender-related themes constituted more than half of the examples provided by their mothers. Intense/obsessional interests in children with GD may be one of the factors underlying the purported link between GD and ASD.