46, XY gonadal dysgenesis: new SRY point mutation in two siblings with paternal germ line mosaicism
Article first published online: 30 JAN 2012
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 82, Issue 6, pages 505–513, December 2012
How to Cite
Stoppa-Vaucher, S., Ayabe, T., Paquette, J., Patey, N., Francoeur, D., Vuissoz, J.-M., Deladoëy, J., Samuels, M., Ogata, T. and Deal, C. (2012), 46, XY gonadal dysgenesis: new SRY point mutation in two siblings with paternal germ line mosaicism. Clinical Genetics, 82: 505–513. doi: 10.1111/j.1399-0004.2011.01832.x
- Issue published online: 6 NOV 2012
- Article first published online: 30 JAN 2012
- Received 30 September 2011, revised and accepted for publication 12 December 2011
- genetic counseling;
- germ line mosaicism;
- SRY point mutation;
- 46, XY complete gonadal dysgenesis;
- 46, XY DSD
Stoppa-Vaucher S, Ayabe T, Paquette J, Patey N, Francoeur D, Vuissoz J-M, Deladoëy J, Samuels ME, Ogata T, Deal CL. 46, XY gonadal dysgenesis: new SRY point mutation in two siblings with paternal germ line mosaicism.
Familial recurrence risks are poorly understood in cases of de novo mutations. In the event of parental germ line mosaicism, recurrence risks can be higher than generally appreciated, with implications for genetic counseling and clinical practice. In the course of treating a female with pubertal delay and hypergonadotropic hypogonadism, we identified a new missense mutation in the SRY gene, leading to somatic feminization of this karyotypically normal XY individual. We tested a younger sister despite a normal onset of puberty, who also possessed an XY karyotype and the same SRY mutation. Imaging studies in the sister revealed an ovarian tumor, which was removed. DNA from the father's blood possessed the wild type SRY sequence, and paternity testing was consistent with the given family structure. A brother was 46, XY with a wild type SRY sequence strongly suggesting paternal Y-chromosome germline mosaicism for the mutation. In disorders of sexual development (DSDs), early diagnosis is critical for optimal psychological development of the affected patients. In this case, preventive karyotypic screening allowed early diagnosis of a gonadal tumor in the sibling prior to the age of normal puberty. Our results suggest that cytological or molecular diagnosis should be applied for siblings of an affected DSD individual.