title: Marfanoid hypermobility caused by an 862 kb deletion of Xq22.3 in a patient with Sotos syndrome.
abstract: Sotos syndrome is a rare genetic disorder characterized by overgrowth associated with macrocephaly and delayed psychomotor development. Patients with Sotos syndrome show 5q35 deletions involving NSD1 or its point mutations. We identified the common 5q35 deletion in a patient with atypical Sotos syndrome manifesting extremely severe developmental delay, joint hypermobility, and skin hyperextensibility, which are recognized as Marfanoid hypermobility syndrome. Further analyses were performed to identify the genetic cause of these additional findings. aCGH analysis revealed an additional 862 kb deletion of Xq22.3 in this patient, which was inherited from his healthy mother. The deleted region included five genes, including the nik-related kinase gene (NRK), which would be a candidate gene for the patient's Marfanoid hypermobility, because it is a member of the glucokinase subfamily that are involved in activating the JNK pathway, and is expressed in developing skeletal musculature. Severe developmental delay seen in the patient may be derived from position effect of the deletion for neighboring interleukin 1 receptor accessory protein-like 2 gene (IL1RAPL2), which is a candidate gene for X-linked mental retardation.
authors.affiliation: Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.forename: Tohru
authors.initials: T
authors.lastname: Okanishi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D001483:Base Sequence; D002648:Child; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D058627:Megalencephaly / Q000235:genetics; D018482:Muscle, Skeletal / Q000002:abnormalities; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011597:Psychomotor Performance; D017422:Sequence Analysis, DNA; D058495:Sotos Syndrome / Q000235:genetics*
chemical_list: C407644:IL1RAPL2 protein, human; D053577:Interleukin-1 Receptor Accessory Protein; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human; C411848:Nik related kinase; D017346:Protein Serine-Threonine Kinases