X-linked mental retardation (XLMR): From clinical conditions to cloned genes

Abstract

X-linked mental retardation (XLMR) is a heterogenous set of conditions responsible for a large proportion of inherited mental retardation. Approximately 200 XLMR conditions and 45 cloned genes are now listed in our catalogue on the Internet at http://xlmr.interfree.it/home.htm. Traditionally, XLMR conditions were subdivided into specific (MRXS) and nonspecific (MRX) forms, depending on their clinical presentation. Now that a growing number of candidate genes have become available for screening XLMR families and patients, this distinction is becoming less useful and similar conditions that had been previously listed as separate can now be grouped together because different mutations in the same gene have been identified. Furthermore, different mutations in the same XLMR gene may account for diseases of increasing severity, but can also cause different phenotypes. As the functions of proteins corresponding to these genes are characterized, biological networks involved in causing mental retardation and conversely in supporting normal intellectual functioning will be discovered. Molecular biologists and neurobiologists will need to cooperate in order to verify the effects of XLMR gene mutations in the context of neuronal circuitry. Eventually, DNA and protein microarray technologies will assist researchers and physicians in reaching a diagnosis even in small families or in individual patients with XLMR.