title: Constitutional delay of growth and puberty is not commonly associated with mutations in the acid labile subunit gene.
abstract: OBJECTIVE
  Constitutional delay of growth and puberty (CDGP) is a common clinical condition that may be inherited as an autosomal dominant, recessive or X-linked trait. However, single-gene defects underlying CDGP have not yet been identified. A small number of children (to date 10) with modest growth failure and in the majority delayed puberty, a phenotype similar to that of CDGP, have been reported to carry mutations in the IGF acid labile subunit (IGFALS) gene which encodes the ALS, a part of the ternary complex carrying IGF-I in the circulation. The aim of our study was to screen a well-characterised CDGP cohort exhibiting a range of growth retardation and pubertal delay for pathogenic sequence variants in IGFALS.
  
  
  METHODS
  We used denaturing high performance liquid chromatography (dHPLC) to screen for IGFALS mutations in DNA samples from 90 children (80 males) with CDGP of predominantly White European origin. DNA fragments generating abnormal waveforms were directly sequenced.
  
  
  RESULTS
  No IGFALS mutation was identified in the coding sequences or exon-intron boundaries in our CDGP cohort. One abnormal waveform pattern in dHPLC in 15 children with CDGP was found to represent a recognised synonymous single-nucleotide polymorphism of the coding transcript in the second exon in residue 210 of IGFALS.
  
  
  CONCLUSIONS
  IGFALS sequence variants are unlikely to be a common association with pubertal delay in children with CDGP.
authors: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Pendlebury, Manchester M27 4HA, UK. indi.banerjee@cmmc.nhs.uk
authors: I
authors: I
authors: Banerjee
authors: D
authors: D
authors: Hanson
authors: R
authors: R
authors: Perveen
authors: A
authors: A
authors: Whatmore
authors: G C
authors: GC
authors: Black
authors: P E
authors: PE
authors: Clayton
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006023:Glycoproteins / Q000235:genetics*; D006130:Growth Disorders / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011628:Puberty, Delayed / Q000150:complications / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C075944:insulin-like growth factor binding protein, acid labile subunit