Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse

  title={Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse},
  author={Michael P Wajnrajch and Joseph M. Gertner and Madeleine D. Harbison and Streamson C. Chua and Rudolph L. Leibel},
  journal={Nature Genetics},
Pituitary growth hormone release is under dual hypothalamic control, stimulated by growth hormone releasing hormone (GHRH) and inhibited by somatostatin. Childhood growth hormone deficiency (GHD), leading to dwarfism and metabolic dysfunction1, can result from a failure of hypothalamic GHRH production or release, from maldevel-opment of the pituitary somatotrophes, and from genetic disorders of growth hormone synthesis. Some familial cases of isolated GHD have been attributed to mutations in… 
Evaluation and Treatment of Adult Growth Hormone Deficiency: An American Endocrine Society Clinical Practice Guideline
1950년대 처음으로 성장호르몬 치료가 시작되었을 때 성 장호르몬은 사람 사체의 뇌하수체로부터 추출하였으며, 한 사람에서 추출된 성장호르몬의 양이 무척 적었기 때문에 공 급이 제한되었다[1]. 추출된 성장호르몬제제는 성장호르몬 결핍증 소아에서 사용되었으며, 1985년에 이 추출물이 Creutzfeldt-Jacob 질환의 발생과의 관련성 때문에 사용이
Contribution à l'étude des bases moléculaires des maladies de la croissance et du mécanisme de régulation du gène GH chez l'homme
Deux mutations heterozygotes composites de LHX3 chez un patient non consanguin ont permis d’assigner a ce gene un syndrome decrit uniquement chez des patients consanguins mais ses cofacteurs ne sont pas connus.
Severe Insulin Resistance and Intrauterine Growth Deficiency Associated With Haploinsufficiency for INSR and CHN2
A likely digenic cause of insulin resistance and growth deficiency resulting from the combined heterozygous disruption of INSR and CHN2 is presented, implicating ChN2 for the first time as a key element of proximal insulin signaling in vivo.
Phenotype and genetic analysis of a syndrome caused by an inactivating mutation in the growth hormone-releasing hormone receptor: Dwarfism of Sindh.
A new form of familial dwarfism is reported, in detail, including its phenotypic features, hormonal profile, and molecular basis, which demonstrates the absolute requirement of GHRH signaling for pituitary GH secretion and postnatal growth in humans, and its relatively minor biological importance in extrapituitary sites.
Extensive phenotypic analysis of a family with growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene.
Molecular investigations revealed a homozygous GHRH-R gene mutation that predicts a severely truncated receptor lacking the seven membrane spanning domains, which is identical to that recently reported in one Indian Moslem family, raising the possibility of a founder effect.
Molecular Genetic Studies in Isolated Growth Hormone Deficiency (IGHD)
Genetic background is more likely in congenital Growth Hormone Deficiency (GHD).
Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice
It is demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2.
Molecular genetics of human growth hormone, insulin-like growth factors and their pathways in common disease
These genes and their associations with disease phenotypes, with special attention to metabolic risk traits are reviewed, and a number of mutations accounting for rare Mendelian disorders have been described in GH-IGF elements.


Effects of a fragment of human growth hormone-releasing factor in normal and 'Little' mice.
Although pituitaries of Little mice contain significant amounts of GH, this pool is not releasable by GRF, which suggests that the dwarfism in Little mice may be partly due to a pituitary defect in GRF receptors or their stimulus-secretion coupling, rather than a deficiency in hypothalamic GRF.
A nonsense mutation of the human luteinizing hormone receptor gene in Leydig cell hypoplasia.
It is demonstrated that functional domains between transmembrane helix 5 and the C-terminal cytoplasmic tail of the hLHR are required for normal cell surface expression of the receptor and signal transduction.
Diagnostic controversy: the diagnosis of childhood growth hormone deficiency revisited.
The aim of this research is to provide a clear picture of the unique needs of children in the developing world and to help policymakers and clinicians better understand these needs.
Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone.
  • K. Mayo
  • Biology, Medicine
    Molecular endocrinology
  • 1992
A mechanism for cellular signaling by GHRH is defined and the opportunity to examine the role of the G HRH receptor in growth abnormalities that involve the GH axis is provided.
Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus.
In the 31 NDI families and 6 families previously reported by us, there is evidence both for mutation hot spots for nucleotide substitutions and for small deletions and insertions, most of which could be attributed to slipped mispairing during DNA replication.
Inherited ateliotic dwarfism in mice. Characteristics of the mutation, little, on chromosome 6.
Because the little mouse shares a number of similarities with the human ateliotic dwarfism, isolated growth hormones deficiency type I, it may be a useful animal model for this inherited human growth disorder.
Growth hormone-releasing hormone.
New insights have been gained with respect to the pathogenesis of both GH deficiency and GH excess states, and the use of GRH and its analogs as diagnostic and therapeutic agents already represents a reality.
Stimulation of growth in the little mouse.
Pituitary dysfunction was confirmed as the basic defect caused by the mutation lit and showed that the GH deficiency is responsible for growth failure, however, the biological site of gene action, the pituitary or hypothalamus, has not been established.