A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor
In: Human molecular genetics (Print), Jg. 14 (2005), Heft 8, S. 1019-1027
Online
academicJournal
- print; 9; 28 ref
Zugriff:
The renin-angiotensin system (RAS) is essential for blood pressure control and water-electrolyte balance. Until the discovery of the renin receptor, renin was believed to be mainly a circulating enzyme with a unique function, the cleavage of angiotensinogen. We report a unique mutation in the renin receptor gene (ATP6AP2) present in patients with X-linked mental retardation and epilepsy (OMIM no. 300423), but absent in 1200 control X-chromosomes. A silent mutation (c.321C>T, p.D107D) residing in a putative exonic splicing enhancer site resulted in inefficient inclusion of exon 4 in 50% of renin receptor mRNA, as demonstrated by quantitative RT-PCR. Analysis of membrane associated-receptor molecular forms showed the presence of full-length and truncated proteins in the patient. Functional analysis demonstrated that the mutated receptor could bind renin and increase renin catalytic activity, similar to the wild-type receptor, but resulted in a modest and reproducible impairment of ERK1/2 activation. Thus, our findings confirm the importance of the RAS in cognitive processes and indicate a novel specific role for the renin receptor in cognitive functions and brain development.
Titel: |
A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor
|
---|---|
Autor/in / Beteiligte Person: | RAMSER, Juliane ; ABIDI, Fatima E ; SCHWARTZ, Charles E ; NGUYEN, Genevieve ; BURCKLE, Celine A ; LENSKI, Claus ; TORIELLO, Helga ; GAIPING, WEN ; LUBS, Herbert A ; ENGERT, Stefanie ; STEVENSON, Roger E ; MEINDL, Alfons |
Link: | |
Zeitschrift: | Human molecular genetics (Print), Jg. 14 (2005), Heft 8, S. 1019-1027 |
Veröffentlichung: | Oxford: Oxford University Press, 2005 |
Medientyp: | academicJournal |
Umfang: | print; 9; 28 ref |
ISSN: | 0964-6906 (print) |
Schlagwort: |
|
Sonstiges: |
|