Familial Neurohypophyseal Diabetes Insipidus—An Update

Christensen, Jane H.; Rittig, Søren

doi:10.1016/j.semnephrol.2006.03.003

Cited by 84 publications

(74 citation statements)

References 159 publications

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“…One potential mechanism is exemplified by mutations in AVP that cause autosomal dominant neurohypophyseal diabetes insipidus because of neurotoxicity of the mutant gene products (reviewed in ref. 41); mutations in GNRH1 may have similar effects. In particular, the R31C mutation in patient 2 could potentially form inappropriate disulfide bonds, resulting in misfolded peptides or aggregates that interfere with the function of the endoplasmic reticulum and cause GnRH neuronal dysfunction.…”

Section: Discussionmentioning

confidence: 99%

GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism

Chan

Guillebon

Lang‐Muritano

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

181

138

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Idiopathic hypogonadotropic hypogonadism (IHH) is a condition characterized by failure to undergo puberty in the setting of low sex steroids and low gonadotropins. IHH is due to abnormal secretion or action of the master reproductive hormone gonadotropin-releasing hormone (GnRH). Several genes have been found to be mutated in patients with IHH, yet to date no mutations have been identified in the most obvious candidate gene, GNRH1 itself, which encodes the preprohormone that is ultimately processed to produce GnRH. We screened DNA from 310 patients with normosmic IHH (nIHH) and 192 healthy control subjects for sequence changes in GNRH1. In 1 patient with severe congenital nIHH (with micropenis, bilateral cryptorchidism, and absent puberty), a homozygous frameshift mutation that is predicted to disrupt the 3 C-terminal amino acids of the GnRH decapeptide and to produce a premature stop codon was identified. Heterozygous variants not seen in controls were identified in 4 patients with nIHH: 1 nonsynonymous missense mutation in the eighth amino acid of the GnRH decapeptide, 1 nonsense mutation that causes premature termination within the GnRH-associated peptide (GAP), which lies C-terminal to the GnRH decapeptide within the GnRH precursor, and 2 sequence variants that cause nonsynonymous amino-acid substitutions in the signal peptide and in GnRH-associated peptide. Our results establish mutations in GNRH1 as a genetic cause of nIHH.GnRH ͉ luteinizing hormone-releasing hormone ͉ LHRH

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Section: Discussionmentioning

confidence: 99%

GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism

Chan

Guillebon

Lang‐Muritano

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

181

138

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“…This hormone acts to regulate the retention of water through increased water reabsorption in the collecting ducts of the nephron. 3 The AVP-NPII gene is an autosomal gene located at 20p13 and is composed of three exons and two introns ( Figure 1A). The 19 amino acid long sequence of the signal peptide and the 9 amino acid long sequence of the AVP moiety are encoded within the first exon.…”

Section: Introductionmentioning

confidence: 99%

“…The 39 amino acid glycopeptide known as copeptin is also encoded within exon 3. 3 The AVP-NPII product, the AVP preprehormone, is produced in the hypothalamus and is targeted to the endoplasmic reticulum (ER) by the signal peptide. Within the ER the signal peptide is removed and the copeptide is glycosylated.…”

Section: Introductionmentioning

confidence: 99%

“…3 Currently, more than 60 mutations affecting AVP-NPII have been associated with FNDI. 1,4 The great majority of FNDI mutations are located within the signal peptide or the NPII moiety of the AVP-NPII gene.…”

Section: Introductionmentioning

confidence: 99%

“…1,4 The great majority of FNDI mutations are located within the signal peptide or the NPII moiety of the AVP-NPII gene. 3,[5][6][7] However, a few cases have been identified of FNDI caused by mutations within the AVP moiety. [8][9][10] In this study, a three-generation Cypriot family with suspected FNDI was investigated by direct sequence of all three AVP-NPII exons to identify potential pathogenic mutations.…”

Section: Introductionmentioning

confidence: 99%

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