We examined the GnRH gene structure in a family with familial central precocious puberty (eight members, four affected) and a family with idiopathic hypogonadotropic hypogonadism (eight members, three affected) using Southern blot analysis and sequencing of cloned polymerase chain reaction products.
We conclude that most cases of IHH in humans do not involve mutations in the GnRH gene and are presumably caused by mutations at one or more other genetic loci that are required for normal function of GnRH-producing neurons.
Denaturing gradient gel electrophoresis failed to identify single-base differences unique to patients with idiopathic hypogonadotropic hypogonadism, dramatically reducing the likelihood that point mutations of the GnRH receptor gene are present in idiopathic hypogonadotropic hypogonadism.
A new compound heterozygous mutation of the gonadotropin-releasing hormone receptor (L314X, Q106R) in a woman with complete hypogonadotropic hypogonadism: chronic estrogen administration amplifies the gonadotropin defect.
To date, 4 genes have been identified as causes of IHH in the human; KAL [the gene for X-linked Kallmann syndrome (IHH and anosmia)], DAX1 [the gene for X-linked adrenal hypoplasia congenita (IHH and adrenal insufficiency)], GNRHR (the GnRH receptor), and PC1 (the gene for prohormone convertase 1, causing a syndrome of IHH and defects in prohormone processing).
To date, 4 genes have been identified as causes of IHH in the human; KAL [the gene for X-linked Kallmann syndrome (IHH and anosmia)], DAX1 [the gene for X-linked adrenal hypoplasia congenita (IHH and adrenal insufficiency)], GNRHR (the GnRH receptor), and PC1 (the gene for prohormone convertase 1, causing a syndrome of IHH and defects in prohormone processing).
A new compound heterozygous mutation of the gonadotropin-releasing hormone receptor (L314X, Q106R) in a woman with complete hypogonadotropic hypogonadism: chronic estrogen administration amplifies the gonadotropin defect.
To date, 4 genes have been identified as causes of IHH in the human; KAL [the gene for X-linked Kallmann syndrome (IHH and anosmia)], DAX1 [the gene for X-linked adrenal hypoplasia congenita (IHH and adrenal insufficiency)], GNRHR (the GnRH receptor), and PC1 (the gene for prohormone convertase 1, causing a syndrome of IHH and defects in prohormone processing).
To date, 4 genes have been identified as causes of IHH in the human; KAL [the gene for X-linked Kallmann syndrome (IHH and anosmia)], DAX1 [the gene for X-linked adrenal hypoplasia congenita (IHH and adrenal insufficiency)], GNRHR (the GnRH receptor), and PC1 (the gene for prohormone convertase 1, causing a syndrome of IHH and defects in prohormone processing).
To date, 4 genes have been identified as causes of IHH in the human; KAL [the gene for X-linked Kallmann syndrome (IHH and anosmia)], DAX1 [the gene for X-linked adrenal hypoplasia congenita (IHH and adrenal insufficiency)], GNRHR (the GnRH receptor), and PC1 (the gene for prohormone convertase 1, causing a syndrome of IHH and defects in prohormone processing).
This case thus expands the emerging clinical spectrum of GnRH-R mutations, provides the first genetic basis for the fertile eunuch variant of IHH and documents the occurrence of reversible IHH in a patient with a GnRH-R mutation.
This case thus expands the emerging clinical spectrum of GnRH-R mutations, provides the first genetic basis for the fertile eunuch variant of IHH and documents the occurrence of reversible IHH in a patient with a GnRH-R mutation.
All patients with complete idiopathic hypogonadotropic hypogonadism had the same GnRHR mutations, but clinical presentations and endocrinologic responses were heterogeneous.