Evolution of gonadotropin deficiency in a patient with type II autosomal dominant GH deficiency

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Evolution of gonadotropin deficiency in a patient with type II autosomal dominant GH deficiency.

BACKGROUND Type II isolated GH deficiency (IGHD type II) is caused by dominant negative splicing or point mutations of the GH-1 gene. Studies have suggested that dominant mutant GH forms prevent the secretion of wild-type GH, resulting in eventual cell death; surprisingly, some patients with these GH mutations develop other hormonal deficiencies (ACTH, TSH). SUBJECTS The proband presented at ...

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An exon splice enhancer mutation causes autosomal dominant GH deficiency.

Familial isolated GH deficiency type II (IGHD II) is caused, in some cases, by heterogeneous IVS3 mutations that affect GH mRNA splicing. We report here our finding an A-->G transition of the fifth base of exon 3 (E3+ 5 A-->G) in affected individuals from an IGHD II family. This mutation disrupts a (GAA)(n) exon splice enhancer (ESE) motif immediately following the weak IVS2 3' splice site. The...

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Prolonged retention after aggregation into secretory granules of human R183H-growth hormone (GH), a mutant that causes autosomal dominant GH deficiency type II.

Human R183H-GH causes autosomal dominant GH deficiency type II. Because we show here that the mutant hormone is fully bioactive, we have sought to locate an impairment in its progress through the secretory pathway as assessed by pulse chase experiments. Newly synthesized wild-type and R183H-GH were stable when expressed transiently in AtT20 cells, and both formed equivalent amounts of Lubrol-in...

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Variability of isolated autosomal dominant GH deficiency (IGHD II): impact of the P89L GH mutation on clinical follow-up and GH secretion.

OBJECTIVE Four distinct familial types of isolated GH deficiency (IGHD) are classified, of which type II, IGHD II, is the autosomal dominant inherited form. Based on clinical data, it became evident that there is a wide variability in phenotype among the various GH-1 gene alterations leading to the disorder. As subjects suffering from IGHD II caused by the specific missense mutated P89L GH (C61...

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Exon splice enhancer mutation (GH-E32A) causes autosomal dominant growth hormone deficiency.

CONTEXT AND OBJECTIVE Alteration of exon splice enhancers (ESE) may cause autosomal dominant GH deficiency (IGHD II). Disruption analysis of a (GAA) (n) ESE motif within exon 3 by introducing single-base mutations has shown that single nucleotide mutations within ESE1 affect pre-mRNA splicing. DESIGN, SETTING, AND PATIENTS Confirming the laboratory-derived data, a heterozygous splice enhancer...

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ژورنال

عنوان ژورنال: European Journal of Endocrinology

سال: 2006

ISSN: 0804-4643,1479-683X

DOI: 10.1530/eje.1.02293