Disease relevance of Coffin-Lowry Syndrome

• The genes responsible for two X-linked diseases, the Coffin-Lowry syndrome (CLS) and juvenile retinoschisis (RS), have been previously mapped, through linkage studies, to an 8-cM region, in Xp22.1-p22.2, flanked distally by two tightly linked markers, DXS207 and DXS43, and proximally by DXS274 [1].
• The Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation characterised in male patients by psychomotor and growth retardation, and various skeletal anomalies [2].
• This review summarizes evidence that disruptions in these pathways are involved in human cognitive disorders, including neurofibromatosis type I, Coffin-Lowry syndrome, Rubinstein-Taybi syndrome, Rett syndrome, tuberous sclerosis-2, Down syndrome, X-linked alpha-thalassemia/mental retardation, cretinism, Huntington disease, and lead poisoning [3].
• Pleiotropy in Coffin-Lowry syndrome: sensorineural hearing deficit and premature tooth loss as early manifestations [4].
• These include neurofibromatosis, tuberous sclerosis, Fragile X syndrome, other inherited forms of mental retardation, cretinism, Coffin-Lowry syndrome, lead poisoning, Rett syndrome, epilepsy, hypoxic-ischemic encephalopathy and cerebral palsy [5].

High impact information on Coffin-Lowry Syndrome

• ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome [6].
• These findings provide direct evidence that abnormalities in the MAPK/RSK signalling pathway cause Coffin-Lowry syndrome [7].
• RSK-2 mutations in humans are linked to Coffin-Lowry syndrome (CLS) [8].
• Cells from a Coffin-Lowry syndrome patient (deficient in RSK2) or expressing an N-terminal or C-terminal kinase-dead mutant of MSK1 were defective for UVB-induced serine 112 phosphorylation of Bad [9].
• Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS) [10].

Chemical compound and disease context of Coffin-Lowry Syndrome

• Abnormal proteodermatan sulfate in three patients with Coffin-Lowry syndrome [11].
• Drop episodes in Coffin-Lowry syndrome: exaggerated startle responses treated with clonazepam [12].
• The 90 kDa ribosomal S6 serine/threonine kinase 2 gene (RSK2, U08316) has been recently identified as a disease-causing gene in an X-linked disorder, the Coffin-Lowry Syndrome (MIM 303600) characterized by severe mental retardation, facial dysmorphisms and progressive skeletal malformations [13].

Biological context of Coffin-Lowry Syndrome

• Unusual splice-site mutations in the RSK2 gene and suggestion of genetic heterogeneity in Coffin-Lowry syndrome [14].
• Unreported RSK2 missense mutation in two male sibs with an unusually mild form of Coffin-Lowry syndrome [15].
• The disease loci for X-linked Retinoschisis (RS), Keratosis follicularis spinulosa decalvans (KFSD), and Coffin-Lowry syndrome (CLS) have been localized to the same, small region in Xp22 on the human X Chromosome (Chr) [16].

Gene context of Coffin-Lowry Syndrome

• The malfunctioning of this system leads to a variety of disorders, ranging from neurological disorders such as Coffin-Lowry syndrome (RSK2 mutations) to cancer (c-fos mutations) [17].
• Three candidate genes in this region were investigated: the cDNA for kinase Rsk-2 involved in Coffin-Lowry syndrome, the brain-specific exon of a transcript in the DMD locus (DP140 isoform of dystrophin), and exon 18 of the glycerol kinase gene, which is specific to fetal brain transcripts [18].
• RSK2 is involved in Coffin-Lowry syndrome and nonspecific MRX [19].
• We report on 7 patients (6 M, 1 F) with Coffin-Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes [4].
• Two other MRX disorders and two syndromal mental retardations, Coffin-Lowry syndrome and Partington syndrome, have been mapped to this region [20].

References