title: Identification and molecular modelling of a novel familial mutation in the SRY gene implicated in the pure gonadal dysgenesis.
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 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.
authors.affiliation: Laboratorio di Citogenetica, Istituto G Gaslini, Genova, Italy. gimcyto@hotmail.com
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gimelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Dimasi
authors.forename: Renata
authors.initials: R
authors.lastname: Bocciardi
authors.forename: Eliana
authors.initials: E
authors.lastname: Di Battista
authors.forename: Tiziano
authors.initials: T
authors.lastname: Pramparo
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D005091:Exons; D005260:Female; D024282:Genes, sry; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics*; D024742:HMG-Box Domains; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051876:Sex-Determining Region Y Protein / Q000737:chemistry
chemical_list: C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein