Variability in anterior pituitary size within members of a family with GH deficiency due to a new splice mutation in the GHRH receptor gene

Maria Alba, Catherine M. Hall, Andrew J. Whatmore, Peter E. Clayton, David A. Price, Roberto Salvatori

    Research output: Contribution to journalArticlepeer-review


    OBJECTIVE: Mutations in the GHRH receptor (GHRHR) gene (GHRHR) cause autosomal recessive isolated GH deficiency (IGHD), and are usually associated with anterior pituitary hypoplasia (APH) (defined as pituitary height more than 2 SDS below normal). We searched for GHRHR mutations and studied pituitary morphology in three prepubertal sibs with severe IGHD, who were born from consanguineous parents. DESIGN: We sequenced the 13 exons and the intronexon boundaries of the GHRHR of the index patient. After identifying a novel mutation, we sequenced the same area in the other family members. In addition, we performed magnetic resonance imaging (MRI) study of the pituitary (at age 8, 4 and 3 years) in the three affected subjects. RESULTS: The three children were homozygous for a new GHRHR mutation that alters the second base of the invariant 5′ splice site (GT) of intron 12 [IVS12 + 2T→A]. The parents and an unaffected sibling were heterozygous for the same change. MRI did not show frank APH (by height criteria) in any of the subjects: pituitary height was normal (5.6 mm, +1.8 SDS) in the oldest sibling, and it was low but not below 2 SDS by age-adjusted criteria in the second (3 mm, -1.4 SDS), and third sibling (2.8 mm, -1.7 SDS). Calculated pituitary volume was below -2 SDS in the youngest patient. CONCLUSIONS: These data demonstrate that pituitary height may fall within 2 SDS from the norm in patients with severe IGHD due to a homozygous GHRHR mutation, and that pituitary size may vary within patients with identical mutations who belong to the same family.
    Original languageEnglish
    Pages (from-to)470-475
    Number of pages5
    JournalClinical Endocrinology
    Issue number4
    Publication statusPublished - Apr 2004


    • Child
    • Child, Preschool
    • Female
    • genetics: Growth Disorders
    • deficiency: Growth Hormone
    • Homozygote
    • Humans
    • Magnetic Resonance Imaging
    • Male
    • Pedigree
    • pathology: Pituitary Gland, Anterior
    • Point Mutation
    • RNA Splice Sites
    • genetics: Receptors, Neuropeptide
    • genetics: Receptors, Pituitary Hormone-Regulating Hormone
    • Sequence Analysis, DNA


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