LIN28B in Constitutional Delay of Growth and Puberty

作者：Tommiska Johanna; Wehkalampi Karoliina; Vaaralahti Kirsi; Laitinen Eeva Maria; Raivio Taneli^*; Dunkel Leo

来源：Journal of Clinical Endocrinology & Metabolism, 2010, 95(6): 3063-3066.

DOI：10.1210/jc.2009-2344

Background: Recently variation in LIN28B, a human ortholog of the gene-regulating processing of micro-RNAs (miRNAs) controlling the timing of major developmental events in the nematode Caenorhabtidis elegans, was reported to be associated with timing of puberty in humans. In C. elegans, a gain-of-function allele of lin-28 causes a retarded phenotype.
Objective: The objective of the study was to evaluate the variation in the LIN28B gene in 145 subjects with constitutional delay of growth and puberty (CDGP).
Patients and Methods: For this study, 115 males and 30 females with CDGP were included. CDGP was defined by Tanner genital or breast stage II and pubertal growth spurt taking place 2 SD later than average. The four coding exons (exons 1-4) and exon-intron boundaries, as well as the fragment of 3' untranslated region containing miRNA recognition elements A and B, of LIN28B were PCR amplified from genomic DNA obtained from peripheral blood leukocytes of the subjects and bidirectionally sequenced.
Results: No variation in the coding region of LIN28B in the 145 subjects with CDGP was found. However, 16 of 145 subjects carried a 2-nucleotide deletion immediately 5' from miRNA recognition element A. These patients did not differ in phenotypic features as compared with noncarriers, and this variant was present in 100 controls with the same frequency.
Conclusions: Our results show that mutations in the coding region or 3' untranslated region miRNA recognition elements A and B of LIN28B do not underlie CDGP. Lack of any variation in the coding region of the gene suggests that LIN28B in developmental timing is so crucial that any changes in the conserved protein would probably be lethal. (J Clin Endocrinol Metab 95: 3063-3066, 2010)

• 出版日期2010-6