Abstract
Y chromosome represents masculinization. The extra Y chromosome of XYY patients usually leads to over-masculinization phenotypes. The occurrence of several DSD cases with XYY in blood is controversial. Is XYY associated with disorder of sex development (DSD)? What is the mechanism behind DSD in males with XYY in blood? To this end, this study retrospectively analyzed blood-karyotype data of 4,437 DSD male children and karyotypes data of 6,259 newborn males as the control. Exome sequencing (ES) was performed to test whether the patients with DSD and with XYY in blood had other variants on known DSD-genes. Testicular biopsy was performed. Fluorescence in situ hybridization (FISH) was used to test whether a sex chromosome mosaicism was present in the oral epithelial cells or gonad tissue of patients with DSD and with XYY in blood. Among 4,437 DSD males who received cytogenetic evaluation, 14 patients with 47,XYY were identified. By contrast, five individuals among the 6,259 controls had 47,XYY. XYY in blood is more frequent among males with DSD than in other males (p = 0.004). The XYY karyotypes were confirmed again by GTG-banding in blood samples and by FISH performed on oral epithelial cells. ES on seven XYY DSD patients was successfully performed, but results did not identify any pathogenic variant on 55 known DSD genes. Gonad biopsy (n = 3) revealed testicular dysplasia and true hermaphroditism. FISH of gonad tissues (n = 3) showed that all of the samples had mosaic for X/XY/XYY. This study is the first to investigate the relationship between XYY in blood and DSD. The knowledge that XYY is in the blood and in oral cells have X/XY/XYY mosaicism in gonadal tissue is new for both researchers and clinicians who seek to understand the genetic basis of DSD males.
Highlights
The diagnosis of chromosome diseases is highly dependent on GTG-binding of blood samples
Patients may vary greatly, ranging from no phenotype and relatively few abnormalities to multi-systemic symptoms; for a specific symptom, the severity can vary among individuals (Kim et al, 2013; Bardsley et al, 2013).Some scholars believe that XYY is associated with a status of over-masculinization, because the existence of an extra Y chromosome and XYY individuals usually results in tall stature, impulsivity, and/or sex organ overdevelopment (Bardsley et al, 2013; Jo et al, 2015)
The claim that XYY males tend to exhibit more aggressive, anti-social, and criminal behavior than XY males is controversial, but this hypothesis has never been substantiated (Lenroot et al, 2009). Another more pointed argument was the opposite of overmasculinization; XYY has been sporadically reported in connection with several cases of disorder of sex development (DSD) (Boczkowski, 1970; Grace and Campbell, 1978; Rivera et al, 1979; Terada et al, 1984; Okamoto et al, 1988; Diego Nuñez et al, 1992; Suzuki et al, 1999; Benasayag et al, 2001; Monastirli et al, 2005; Bardsley et al, 2013; Latrech et al, 2015)
Summary
The diagnosis of chromosome diseases is highly dependent on GTG-binding of blood samples. The claim that XYY males tend to exhibit more aggressive, anti-social, and criminal behavior than XY males is controversial, but this hypothesis has never been substantiated (Lenroot et al, 2009) Another more pointed argument was the opposite of overmasculinization; XYY has been sporadically reported in connection with several cases of disorder of sex development (DSD) (Boczkowski, 1970; Grace and Campbell, 1978; Rivera et al, 1979; Terada et al, 1984; Okamoto et al, 1988; Diego Nuñez et al, 1992; Suzuki et al, 1999; Benasayag et al, 2001; Monastirli et al, 2005; Bardsley et al, 2013; Latrech et al, 2015). Given that more than half of patients with DSD can be traced to a pathogenic variant on one of 55 known genes related to DSD (Eggers et al, 2016; Wang et al, 2017), it is possible that the DSD phenotypes are the consequence of an extra Y chromosome and a pathogenic variant on one of the known DSD genes
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