BES2005 Poster Presentations Growth and development (48 abstracts)
Constitutional delay of growth and puberty (CDGP)is associated with the GPR54 gene but not with Leptin (L), Leptin Receptor (LR) and Cocaine and Amphetamin Regulated Transcript (CART) genes
I Banerjee 1 , J Trueman 2 , L Patel 2 , CM Hall 1 , DA Price 1 , JN Hirschhorn 4 , MR Palmert 4 , A Read 3 & PE Clayton 2
1Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK; 2Endocrine Science Research Group, University of Manchester, Manchester, UK; 3Academic Unit of Medical Genetics, University of Manchester, UK; 4Division of Paediatric Endocrinology and Metabolism, University Hospitals of Cleveland, USA.
CDGP is a common growth disorder, often dominantly inherited. Genetic association is thus very likely. There are many possible candidates but none are yet linked to CDGP. We assessed the possible contribution of L, LR genes (mutations in each cause very delayed or absent puberty), CART (mediates the effect of L on GnRH pulse generation), and GPR54 (a hypothalamic G-protein coupled receptor, which is mutated in familial hypogonadotrophic hypogonadism) genes.
Approval was obtained from the local research ethics committee. Two approaches were undertaken: (1) Genotyping for recognised polymorphisms (L - 3' CTTT repeat, LR - Gly>Arg substitution in exon 6) and (2) screening the whole gene for novel polymorphisms by denaturing high performance liquid chromatography (DHPLC) for CART and MassARRAY for GPR54. Analysis was undertaken in 89 CDGP subjects and their parents and in 113 healthy controls. Association was tested both by genotype frequency in cases versus controls and by transmission disequilibrium testing (Tdt).
The frequency of the L CTTT repeat (short versus long) and the LR alleles did not differ between cases and controls, nor was there significant bias in the Tdt. An adenine deletion was identified in exon 3 of CART; its frequency in CDGP was 12% and 7% in controls (p=0.1). However in GPR54, polymorphic markers 15kB upstream of the coding sequence showed preferential transmission of one allele at a 2:1 ratio in males (p=0.03 and 0.06 for the 2 linked markers).
Sequence variations in the L, LR and CART genes are not associated with CDGP. Polymorphisms upstream of the GPR54 gene may be linked to CDGP and may contribute to the tempo of growth and pubertal development, but this needs confirmation in other cohorts.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more