Metherell L A, Akker S A, Munroe P B, Rose S J, Caulfield M, Savage M O, Chew S L, Clark A J
Department of Chemical Endocrinology, St. Bartholomew's Hospital, London EC1A 7BE, United Kingdom.
Am J Hum Genet. 2001 Sep;69(3):641-6. doi: 10.1086/323266. Epub 2001 Jul 20.
Inherited growth-hormone insensitivity (GHI) is a heterogeneous disorder that is often caused by mutations in the coding exons or flanking intronic sequences of the growth-hormone receptor gene (GHR). Here we describe a novel point mutation, in four children with GHI, that leads to activation of an intronic pseudoexon resulting in inclusion of an additional 108 nt between exons 6 and 7 in the majority of GHR transcripts. This mutation lies within the pseudoexon (A(-1)-->G(-1) at the 5' pseudoexon splice site) and, under in vitro splicing conditions, results in inclusion of the mutant pseudoexon, whereas the wild-type pseudoexon is skipped. The presence of the pseudoexon results in inclusion of an additional 36-amino acid sequence in a region of the receptor known to be involved in homo-dimerization, which is essential for signal transduction.
遗传性生长激素不敏感（GHI）是一种异质性疾病，通常由生长激素受体基因（GHR）编码外显子或侧翼内含子序列的突变引起。在此，我们描述了4例GHI患儿中的一种新型点突变，该突变导致一个内含子假外显子激活，致使大多数GHR转录本在第6和第7外显子之间额外插入108个核苷酸。此突变位于假外显子内（5'假外显子剪接位点处的A（-1）→G（-1）），在体外剪接条件下，会导致突变假外显子的包含，而野生型假外显子则被跳过。假外显子的存在导致受体中已知参与同源二聚化区域额外包含36个氨基酸序列，同源二聚化对信号转导至关重要。
