Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.

Abstract:

:The Coffin-Lowry syndrome (CLS), an X-linked disorder, is characterized by severe psychomotor retardation, facial and digital dysmorphisms, and progressive skeletal deformations. Genetic linkage analysis mapped the CLS locus to an interval of 2-3 megabases at Xp22.2. The gene coding for Rsk-2, a member of the growth-factor-regulated protein kinases, maps within the candidate interval, and was tested as a candidate gene for CLS. Initial screening for mutations in the gene for Rsk-2 in 76 unrelated CLS patients revealed one intragenic deletion, a nonsense, two splice site, and two missense mutations. The two missenses affect sites critical for the function of Rsk-2. The mutated Rsk-2 proteins were found to be inactive in a S6 kinase assay. These findings provide direct evidence that abnormalities in the MAPK/RSK signalling pathway cause Coffin-Lowry syndrome.

journal_name

Nature

journal_title

Nature

authors

Trivier E,De Cesare D,Jacquot S,Pannetier S,Zackai E,Young I,Mandel JL,Sassone-Corsi P,Hanauer A

doi

10.1038/384567a0

subject

Has Abstract

pub_date

1996-12-12 00:00:00

pages

567-70

issue

6609

eissn

0028-0836

issn

1476-4687

journal_volume

384

pub_type

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