Autosomal recessive form of isolated growth hormone deficiency is more frequent than the autosomal dominant form in a Brazilian cohort

Lido, Andria C.V.; França, Marcela M.; Correa, Fernanda A.; Otto, Aline P.; Carvalho, Luciani R.; Quedas, Elisangela P S; Nishi, Mirian Yumie; Mendonca, Berenice B.; Arnhold, Ivo Jorge Prado; Jorge, Alexander A L

doi:10.1016/j.ghir.2014.07.001

Cited by 4 publications

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“…The molecular diagnosis of the index patient was previously described by Lido and cols. (13), with the allelic variant c.291+1G> T in the GH1 gene in heterozygosis by Sanger sequencing. The patient's mother was studied, and no mutation was found.…”

Section: Case Reportmentioning

confidence: 99%

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Cushing disease due to a somatic USP8 mutation in a patient with evolving pituitary hormone deficiencies due to a germline GH1 splicing variant

Labello¹,

Benedetti²,

Azevedo³

et al. 2022

Archives of Endocrinology and Metabolism

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We present the unique case of an adult Brazilian woman with severe short stature due to growth hormone deficiency with a heterozygous G to T substitution in the donor splice site of intron 3 of the growth hormone 1 (GH1) gene (c.291+1G>T). In this autosomal dominant form of growth hormone deficiency (type II), exon 3 skipping results in expression of the 17.5 kDa isoform of growth hormone, which has a dominant negative effect over the bioactive isoform, is retained in the endoplasmic reticulum, disrupts the Golgi apparatus, and impairs the secretion of other pituitary hormones in addition to growth hormone deficiency. This mechanism led to the progression of central hypothyroidism in the same patient. After 5 years of growth and thyroid hormone replacement, at the age of 33, laboratory evaluation for increased weight gain revealed high serum and urine cortisol concentrations, which could not be suppressed with dexamethasone. Magnetic resonance imaging of the sella turcica detected a pituitary macroadenoma, which was surgically removed. Histological examination confirmed an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma. A ubiquitin-specific peptidase 8 (USP8) somatic pathogenic variant (c.2159C>G/p.Pro720Arg) was found in the tumor. In conclusion, we report progression of isolated growth hormone deficiency due to a germline GH1 variant to combined pituitary hormone deficiency followed by hypercortisolism due to an ACTH-secreting macroadenoma with a somatic variant in USP8 in the same patient. Genetic studies allowed etiologic diagnosis and prognosis of this unique case.

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Section: Case Reportmentioning

confidence: 99%

“…(13) identified pathogenic GH1 defects in 9 patients with IGHD, eight with the autosomal recessive form, and one with the autosomal dominant form. The latter patient had a heterozygous nucleotide substitution in the first nucleotide of intron 3 (c.291+1G>T) (13).…”

Section: Introductionmentioning

confidence: 97%