Homozygous HESX1 and COL1A1 Gene Variants in a Boy with Growth Hormone Deficiency and Early Onset Osteoporosis

Int J Mol Sci. 2021 Jan 13;22(2):750. doi: 10.3390/ijms22020750.


We report on a patient born to consanguineous parents, presenting with Growth Hormone Deficiency (GHD) and osteoporosis. SNP-array analysis and exome sequencing disclosed long contiguous stretches of homozygosity and two distinct homozygous variants in HESX1 (Q6H) and COL1A1 (E1361K) genes. The HESX1 variant was described as causative in a few subjects with an incompletely penetrant dominant form of combined pituitary hormone deficiency (CPHD). The COL1A1 variant is rare, and so far it has never been found in a homozygous form. Segregation analysis showed that both variants were inherited from heterozygous unaffected parents. Present results further elucidate the inheritance pattern of HESX1 variants and recommend assessing the clinical impact of variants located in C-terminal propeptide of COL1A1 gene for their potential association with rare recessive and early onset forms of osteoporosis.

Keywords: COL1A1; CPHD; E1361K; HESX1; Q6H; combined pituitary hormone deficiency; osteoporosis.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Age of Onset
  • Amino Acid Substitution
  • Collagen Type I / chemistry
  • Collagen Type I / genetics*
  • DNA Mutational Analysis
  • Facies
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics*
  • Homozygote*
  • Human Growth Hormone / deficiency*
  • Humans
  • Hypopituitarism / complications
  • Hypopituitarism / genetics
  • Magnetic Resonance Imaging
  • Male
  • Models, Molecular
  • Mutation*
  • Osteoporosis / diagnosis*
  • Osteoporosis / etiology*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Radiography
  • Structure-Activity Relationship


  • Collagen Type I
  • HESX1 protein, human
  • Homeodomain Proteins
  • collagen type I, alpha 1 chain
  • Human Growth Hormone