title: A novel homozygous mutation of the IGFALS gene in a female adolescent: indirect evidence for a contributing role of the circulating IGF-I pool in the pubertal growth spurt.
abstract: BACKGROUND
  Mutations of the IGFALS gene have been reported since 2004 in 24 patients, but only 5 of these are females.
  
  
  METHODS
  We describe a 14.7-year-old female of a consanguineous Moroccan family with growth retardation and normal-onset but slow progression of puberty without manifest pubertal height gain.
  
  
  RESULTS
  At age 3.2 years, the patient's height was 85.5 cm (-2.9 SDS) and her weight 9.9 kg (-2.9 SDS) with a head circumference of 44.5 cm (-3.3 SDS). Serum IGF-I and IGFBP-3 concentrations were low with normal basal and stimulated growth hormone (GH) levels. An IGF-I generation test confirmed a lack of response to GH administration. While onset of puberty occurred at a normal age, no significant pubertal growth acceleration was observed despite progression of breast development. Sequencing of the IGFALS gene revealed a novel homozygous frameshift mutation (c.1291delT) with a stop codon (p.W431GfsX10) leading to undetectable serum levels of acid-labile subunit.
  
  
  CONCLUSIONS
  We report the phenotype of an adolescent girl with primary IGF-I deficiency due to a novel homozygous mutation of the IGFALS gene, who presented with growth delay, normal pubertal onset with slow progression and no pubertal growth acceleration indirectly suggesting a contributing role of the circulating IGF-I pool in the pubertal growth spurt.
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Thekla
authors.initials: T
authors.lastname: Poukoulidou
authors.forename: Julia
authors.initials: J
authors.lastname: Kowalczyk
authors.forename: Lou
authors.initials: L
authors.lastname: Metherell
authors.forename: Jean
authors.initials: J
authors.lastname: De Schepper
authors.forename: Marc
authors.initials: M
authors.lastname: Maes
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D016368:Frameshift Mutation; D006023:Glycoproteins / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics* / Q000503:physiopathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D012741:Sexual Maturation / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I