title: A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation.
abstract: Large deletions in Xq21 often are associated with contiguous gene syndromes consisting of X-linked deafness type 3 (DFN3), mental retardation (MRX), and choroideremia (CHM). The identification of deletions associated with classic CHM or DFN3 facilitated the positional cloning of the underlying genes, REP-1 and POU3F4, respectively, and enabled the positioning of the MRX gene in between these genes. Here, we report the cloning and characterization of a novel gene, ribosomal S6-kinase 4 (RSK4; HGMW-approved symbol RPS6KA6), which maps in the MRX critical region. RSK4 is completely deleted in eight patients with the contiguous gene syndrome including MRX, partially deleted in a patient with DFN3 and present in patients with an Xq21 deletion and normal intellectual abilities. RSK4 is most abundantly expressed in brain and kidney. The predicted protein of 746 amino acids shows a high level of homology to three previously isolated members of the human RSK family. RSK2 is involved in Coffin-Lowry syndrome and nonspecific MRX. The localization of RSK4 in the interval that is commonly deleted in mentally retarded males together with the high degree of amino acid identity with RSK2 suggests that RSK4 plays a role in normal neuronal development. Further mutation analyses in males with X-linked mental retardation must prove that RSK4 is indeed a novel MRX gene.
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, Nijmegen, 6500 HB, The Netherlands.
authors.forename: H G
authors.initials: HG
authors.lastname: Yntema
authors.forename: B
authors.initials: B
authors.lastname: van den Helm
authors.forename: J
authors.initials: J
authors.lastname: Kissing
authors.forename: G
authors.initials: G
authors.lastname: van Duijnhoven
authors.forename: F
authors.initials: F
authors.lastname: Poppelaars
authors.forename: J
authors.initials: J
authors.lastname: Chelly
authors.forename: C
authors.initials: C
authors.lastname: Moraine
authors.forename: J P
authors.initials: JP
authors.lastname: Fryns
authors.forename: B C
authors.initials: BC
authors.lastname: Hamel
authors.forename: H
authors.initials: H
authors.lastname: Heilbronner
authors.forename: H J
authors.initials: HJ
authors.lastname: Pander
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: H H
authors.initials: HH
authors.lastname: Ropers
authors.forename: F P
authors.initials: FP
authors.lastname: Cremers
authors.forename: H
authors.initials: H
authors.lastname: van Bokhoven
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015794:Choroideremia / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D015870:Gene Expression; D005820:Genetic Testing; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010770:Phosphotransferases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D038601:Ribosomal Protein S6; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics*; D012269:Ribosomal Proteins / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014960:X Chromosome / Q000235:genetics
chemical_list: D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D010770:Phosphotransferases; D019893:Ribosomal Protein S6 Kinases