Recurrent Deletion of ZNF630 at Xp11.23 Is Not Associated With Mental Retardation

Lugtenberg, D.; Zangrande-Vieira, L.; Kirchhoff, M.; Whibley, A.C.; Oudakker, A.R.; Kjaergaard, S.; Vianna-Morgante, A.M.; Kleefstra, T.; Ruiter, M.; Jehee, F.S.; Ullmann, R.; Schwartz, C.E.; Stratton, M.; Raymond, F.L.; Veltman, J.A.; Vrijenhoek, T.; Pfundt, R.; Schuurs-Hoeijmakers, J.H.M.; Hehir-Kwa, J.Y.; Froyen, G.; Chelly, J.; Ropers, H.H.; Moraine, C.; Gecz, J.; Knijnenburg, J.; Kant, S.G.; Hamel, B.C.J.; Rosenberg, C.; Bokhoven, H. van; Brouwer, A.P.M. de

doi:doi:10.1002/ajmg.a.33292

ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P-value = 0.174). Conversely, a 1.9-fold lower frequency of ZNF630 duplications was observed...Show moreZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P-value = 0.174). Conversely, a 1.9-fold lower frequency of ZNF630 duplications was observed in patients, which was not significant either (P-value = 0.163). These data do not show that ZNF630 deletions or duplications are associated with mental retardation. (C) 2010 Wiley-Liss, Inc.Show less

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Recurrent Deletion of ZNF630 at Xp11.23 Is Not Associated With Mental Retardation