ESPE Abstracts

Background: Steroidogenic factor 1 (SF1), encoded by the gene NR5A1, is a member of the orphan nuclear receptor superfamily and important regulator of gonadal and adrenal function. Variations in SF1 lead to a spectrum of conditions including 46,XY DSD, hypospadias, adrenal insufficiency, male factor infertility, and primary ovarian insufficiency. Inheritance patterns can be complicated (e.g. de novo dominant, sex-limited dominant, and autosomal recessive). Information currently available on SF1 is generally not easily accessible for patients and families or healthcare professionals not working in the field.

Objective and hypotheses: To make available a database of the published variants of SF1 together with general information about SF1 through a website www.steroidogenicfactor-1.info.

Method: A systematic review of published mutations in SF1 since 1999 was undertaken using a basic literature search. Information regarding the variant and phenotypic information was entered onto a database. General information about SF1, associated features, inheritance patterns, and key resources was developed as a web-based format.

Results: To date there are 62 primary peer reviewed publications in the SF1 database and more than 100 potentially disease associated variants. These findings have been summarized in a schematic figure to illustrate the amino acid residue variants and conditions associated with them. Approximately two-thirds of SF1 variants are missense changes. There is an emerging clustering of DSD-related changes in the DNA-binding domain and key codons within the ligand-like binding domain, whereas male factor infertility-associated variants cluster within the hinge region. A website has been set up to host this database as well as useful information about SF1available for patients and the public.

Conclusion: SF1/NR5A1 is an ever important cause of endocrine disorders with diverse phenotypes and inheritance patterns. Development of ‘www.sterodiogenicfactor-1.info’ will assist researchers, clinicians, patients, and families with background knowledge, phenotypic and genetic information, and related resources for support.

Funding: This work was supported by The Wellcome Trust (098513).