| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
We analyzed GH-1 gene from 20 GH deficiency patients (severe or mild short stature) that an agreement of a family and oneself acquired what intron of a GH-1 gene included it and paid attention to important location and intron splice enhancer (ISE) motif thought about in splicing, and a gene analyzed for a purpose.
Familial isolated GH deficiency type II (IGHD-II) is an autosomal dominant inheritant disorder that has been recently shown in some patients to be caused by heterogeneous mutants at the intron 3 of the GH-1 gene.
We report a family which includes two affected members, mother and daughter, whereas father and brother are of normal height. Diagnosis of GHD was based on the clinical features, growth retardation, and minimal GH response to GH stimulation tests. We started GH replacement therapy for the daughter at 8 years old and a good response has been following. In this case the sequenceanalyses of the GH-1 gene in mother and daughter revealed a heterozygous mutation for a G→A transition in the 28th base of the donor splice site of intron 3. The mutation resides in intron splice enhancer (ISE) motif and may perturb the regulation of splicing of pre-mRNA that caused exon 3 skipping, resulting in truncated hGH product that is supposed to prevent secretion of normal hGH in the pituitary cells.
It was a result, but we struck the GH-1 gene from 20 GH deficiency patients that we analyzed, and the thing with abnormally of the intron 3 was not recognized. About ISE motif of other intron, intron including abnormality of base arrangement partially was confirmed, but whether they are the same mechanism to our report and are indistinct about significance of illness. There are not clinical differences, but makes them with our future problems.
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