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Gene Diagnosis of Idiopathic Hypogonadotropic Hypogonadism and Initial Function Study of Pathogenic Mutation

Author: GuoJian
Tutor: ZuoLingQian
School: Central South University
Course: Genetics
Keywords: Kallmann syndrome KAL1 gene PROKR2 gene PROKR2 gene function
CLC: R588
Type: Master's thesis
Year: 2011
Downloads: 16
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Abstract

Background: Idiopathic (simple) decreased gonadotropin-gonadal function (Isolated hypogonadotropic hypogonadism, IHH) is the synthesis and secretion of hypothalamic gonadotropin-releasing hormone (GnRH) defects resulting in simple pituitary gonadotropin secretion caused by hypogonadism. Kallmann syndrome (Kallmann syndrome, KS) showed a congenital promote a joint show symptoms of hypogonadism and anosmia, accounting for 60% of the incidence of IHH, it is sometimes associated with other illnesses, such as eye mirror movement , cleft palate and kidney hypoplasia. KS is a genetically heterogeneous disease, the incidence rate for males 1/8000, 1/50000 women. The incidence of KS may be the result of one or more of the associated gene mutations. These genes include genes involved in recessive X-linked inheritance KAL1 It is located in Xp22.3. Involved in autosomal dominant fibroblast growth factor receptor 1 gene (fibroblast Growth Factor receptor 1, FGFR1). Before dynein receptor 2 gene (Prokineticin receptor2 Gene PROKR2) and former dynein gene (gene Prokineticin PROK2), most of them hybrid mutations cause disease. However, currently found in these genes explain only 30% of the cause of KS. Objective: 18 the IHH patients undergoing genetic testing, in order to discover their potential disease-causing gene mutation on a gene mutation detected preliminary functional studies. Next IHH accurate diagnosis of the patient, and even prenatal diagnosis lay a theoretical foundation. Methods: five KS gene mutation screening using PCR and DNA sequencing technology, these genes include FGFR1 fibroblast growth factor 8 (fibroblast growth factor 8, FGF8), PROKR2, PROK2 KAL1 finally create the associated mutations the model functional analysis. Results: (1) KAL1, FGFR1, FGF8 has been implicated as a negative player, none of PROK2 gene detected disease-causing mutations. (2) PROKR2 gene has three types of mutations were found: 991 G gt; A, 533 G gt; C and 151 g gt; A Gt; 991 G A mutation was found in 2 people, it leads to the first 331 amino acids encoded by the valine to methionine; 533 G gt; C mutation in 1 people found, which led to 178 mutated to serine amino acid tryptophan. 151 G GT; A mutation was found in 3 people, it leads to the first 51 amino acids from alanine mutation into threonine, which is a new mutations have not been reported. The rest of the patient is not detected (?) Gene mutations PROKR2. (3) 151 G gt; A weakened a PROKR2 of signal transduction, resulting in decrease in intracellular Ca2 release. Conclusions: (1) at the gene level diagnostic c.991 G GT; A, c.533 G gt; C, c.151 G gt; A mutation is the causative mutation leads to a patient suffering from Kallmann syndrome. C.151 G gt; A mutation for new mutations have not been reported, which extends the mutation spectrum of PROKR2, clarify disease etiology and PROKR2 of mutations effect. (2) have not been reported c.151 G gt; A mutation weakened signal transduction of PROKR2, is the main cause Kallmann syndrome occurs.

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