title: LIN28B in constitutional delay of growth and puberty.
abstract: 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 Caenorhabditis 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).
  
  
  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.
authors.affiliation: Institute of Biomedicine, Department of Physiology, University of Helsinki, Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8), University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tommiska
authors.forename: Karoliina
authors.initials: K
authors.lastname: Wehkalampi
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vaaralahti
authors.forename: Eeva-Maria
authors.initials: EM
authors.lastname: Laitinen
authors.forename: Taneli
authors.initials: T
authors.lastname: Raivio
authors.forename: Leo
authors.initials: L
authors.lastname: Dunkel
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006128:Growth / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D011627:Puberty / Q000235:genetics / Q000502:physiology; D011628:Puberty, Delayed / Q000235:genetics*; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins