1. ¹Laboratorio di Citogenetica, Istituto G Gaslini, Genova, Italy
2. ²Biologia Generale e Genetica Medica, Università di Pavia, Pavia, Italy
3. ³Laboratorio di Medicina Molecolare, Istituto G Gaslini, Genova, Italy
4. ⁴Laboratorio di Genetica Molecolare, Istituto G Gaslini, Genova, Italy
5. ⁵DIPE, Università di Genova, Istituto G Gaslini, Genova, Italy

Correspondence: Dr G Gimelli, Laboratorio di Citogenetica, Istituto G Gaslini, L.go G.Gaslini 5, I-16148 Genova, Italy. Tel: +39 010 5636371; Fax: +39 010 382639; E-mail: gimcyto@hotmail.com

Received 15 May 2006; Revised 19 July 2006; Accepted 15 August 2006; Published online 25 October 2006.

Abstract

SRY gene is responsible for initiating male sexual differentiation. The protein encoded by SRY contains a homeobox (HMG) domain, which is a DNA-binding domain. Mutations of the SRY gene are reported to be associated with XY pure gonadal dysgenesis. The majority of these are de novo mutations affecting only one individual in a family. Only a small subset of mutations is shared between the father and one or more of his children. Most of these familial mutations are localized within the HMG box and only two are at the N-terminal domain of the SRY protein. Herein, we describe a young girl with pure gonadal dysgenesis and her father carrying a novel familial mutation in the SRY gene at codon number 3. This mutation is resulting in a serine (S) to leucine (L) substitution. The secondary structure of the SRY protein was carried out by protein modelling studies. This analysis suggests, with high possibility, that the N-terminal domain of the SRY protein, where we found the mutation, could form an -helix from amino acid in position 2 to amino acid in position 13. The secondary structure prediction and the chemical properties of serine to leucine substitution stands for a potential disruption of this N-terminal -helix in the SRY protein. This mutation could have some role in impeding the normal function of the SRY protein.