Details

Autor(en) / Beteiligte

• Metherell, Louise A.
• Akker, Scott A.
• Munroe, Patricia B
• Rose, Stephen J
• Caulfield, Mark
• Savage, Martin O.
• Chew, Shern L.
• Clark, Adrian J.L.

Titel

Pseudoexon Activation as a Novel Mechanism for Disease Resulting in Atypical Growth-Hormone Insensitivity

Ist Teil von

• American journal of human genetics, 2001-09, Vol.69 (3), p.641-646

Ort / Verlag

Chicago, IL: Elsevier Inc

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.