title: Four novel RSK2 mutations in females with Coffin-Lowry syndrome.
abstract: Coffin-Lowry syndrome (CLS) is an X-linked semi-dominant disorder caused by mutations in the RSK2 gene and characterized by moderate to severe mental retardation, characteristic facial features, skeletal deformities, and tapering fingers in males. Females are usually much more mildly and variably affected thus more difficult to diagnose. In this study, molecular genetic analysis was carried out in four female patients presenting features of Coffin-Lowry syndrome. The probands were sporadic cases with no affected males in their families. The molecular analysis of the RSK2 gene revealed four novel mutations, including two frameshift and one missense mutation identified by sequencing, and one large deletion detected by multiplex ligation-dependent probe amplification (MLPA) analysis. Females exhibited a random X-chromosome inactivation pattern. To our knowledge, this is the first report of applying MLPA in the diagnostics of CLS and the first description of a large deletion in a CLS female. These results support including screening for large rearragements in the genetic analysis of female CLS patients.
authors.affiliation: Children's Memorial Health Institute, Department of Medical Genetics, Warsaw, Poland. d.jurkiewicz@czd.pl
authors.forename: Dorota
authors.initials: D
authors.lastname: Jurkiewicz
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jezela-Stanek
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Ciara
authors.forename: Dorota
authors.initials: D
authors.lastname: Piekutowska-Abramczuk
authors.forename: Monika
authors.initials: M
authors.lastname: Kugaudo
authors.forename: Maria
authors.initials: M
authors.lastname: Gajdulewicz
authors.forename: Krystyna
authors.initials: K
authors.lastname: Chrzanowska
authors.forename: Ewa
authors.initials: E
authors.lastname: Popowska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D038921:Coffin-Lowry Syndrome / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D021141:Nucleic Acid Amplification Techniques; D010641:Phenotype; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics*; D049951:X Chromosome Inactivation
chemical_list: D019893:Ribosomal Protein S6 Kinases