1. ¹Genetics Service, Centre de Diagnòstic Biomèdic, Hospital Clínic, Barcelona, Spain
2. ²IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
3. ³Neurology Service, Hospital Sant Joan de Déu, Barcelona, Spain

Correspondence: Dr M Milà, Genetics Service, Hospital Clínic, C/Villarroel, 170 08036 Barcelona, Spain. Tel: +34 93 227 54 00 ext. 2784; Fax: +34 93 451 52 72; E-mail: mmila@clinic.ub.es

^†These two authors contributed equally to this work.

Received 16 November 2005; Revised 9 February 2006; Accepted 10 February 2006; Published online 15 March 2006.

Abstract

X-linked mental retardation (XLMR) is an extremely heterogeneous condition that account for 15–25% of all mentally retarded patients. The number of genes newly reported in relation with this condition has been rapidly increased in the past years. One of the latest is called Jumonji AT-rich interactive domain 1C (JARID1C). This gene encodes for a member of a recently discovered protein family that harbours DNA-binding motifs, suggesting a possible role in transcriptional regulation and in the modification of chromatin structure. In this work we describe the results obtained by screening JARID1C gene in 24 mentally retarded males with history of at least two affected males. Remarkably, we have found a novel missense mutation in exon 10 of the gene that results in a Serine-to-arginine change at amino-acid 451 (S451R). This nucleotide change appears to be restricted to mentally retarded patients, since it has not been detected in control samples. Familial analysis has confirmed the segregation of this mutation with mental retardation. Furthermore, sequence alignment analysis with the different members of the human JARID1 family and with homologous proteins of mouse and fruit fly has revealed that the affected amino acid is conserved. Our data highlights the importance of reporting mutations in this gene since it might support the recent findings that implicates JARID1C with XLMR.