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Eur J Hum Genet. 2007 Jan;15(1):76-80. Epub 2006 Oct 25.

Identification and molecular modelling of a novel familial mutation in the SRY gene implicated in the pure gonadal dysgenesis.

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Laboratorio di Citogenetica, Istituto G Gaslini, Genova, Italy.


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 alpha-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 alpha-helix in the SRY protein. This mutation could have some role in impeding the normal function of the SRY protein.

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