SRPX2 mutations in disorders of language cortex and cognition.
نویسندگان
چکیده
The rolandic and sylvian fissures divide the human cerebral hemispheres and the adjacent areas participate in speech processing. The relationship of rolandic (sylvian) seizure disorders with speech and cognitive impairments is well known, albeit poorly understood. We have identified the Xq22 gene SRPX2 as being responsible for rolandic seizures (RSs) associated with oral and speech dyspraxia and mental retardation (MR). SRPX2 is a secreted sushi-repeat containing protein expressed in neurons of the human adult brain, including the rolandic area. The disease-causing mutation (N327S) resulted in gain-of-glycosylation of the secreted mutant protein. A second mutation (Y72S) was identified within the first sushi domain of SRPX2 in a male with RSs and bilateral perisylvian polymicrogyria and his female relatives with mild MR or unaffected carrier status. In cultured cells, both mutations were associated with altered patterns of intracellular processing, suggesting protein misfolding. In the murine brain, Srpx2 protein expression appeared in neurons at birth. The involvement of SRPX2 in these disorders suggests an important role for SRPX2 in the perisylvian region critical for language and cognitive development.
منابع مشابه
The human language-associated gene SRPX2 regulates synapse formation and vocalization in mice.
Synapse formation in the developing brain depends on the coordinated activity of synaptogenic proteins, some of which have been implicated in a number of neurodevelopmental disorders. Here, we show that the sushi repeat-containing protein X-linked 2 (SRPX2) gene encodes a protein that promotes synaptogenesis in the cerebral cortex. In humans, SRPX2 is an epilepsy- and language-associated gene t...
متن کاملEpileptic and developmental disorders of the speech cortex: ligand/receptor interaction of wild-type and mutant SRPX2 with the plasminogen activator receptor uPAR.
Mutations in SRPX2 (Sushi-Repeat Protein, X-linked 2) cause rolandic epilepsy with speech impairment (RESDX syndrome) or with altered development of the speech cortex (bilateral perisylvian polymicrogyria). The physiological roles of SRPX2 remain unknown to date. One way to infer the function of SRPX2 relies on the identification of the as yet unknown SRPX2 protein partners. Using a combination...
متن کاملMolecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex.
It is a challenge to identify the molecular networks contributing to the neural basis of human speech. Mutations in transcription factor FOXP2 cause difficulties mastering fluent speech (developmental verbal dyspraxia, DVD), whereas mutations of sushi-repeat protein SRPX2 lead to epilepsy of the rolandic (sylvian) speech areas, with DVD or with bilateral perisylvian polymicrogyria. Pathophysiol...
متن کاملChanges of the brain’s bioelectrical activity in cognition, consciousness, and some mental disorders
Background: An electroencephalogram (EEG) is an accepted method in neurophysiology with a wide application. Different types of brain rhythms indicate that simultaneous activity of the brain cortex neurons depend on the person’s mental state. Method: we have focus on reviewing the existing literature pertaining to changes of the brain’s bioelectrical activity that recorded from the ...
متن کاملModulation of Drug Craving in Crystalline-Heroin Users by Transcranial Direct Current Stimulation of Dorsolateral Prefrontal Cortex
Background: Drug craving, the main cause of relapse and a major motivator for drug use, is a challenging obstacle in substance use treatment. Transcranial direct current stimulation (tDCS), a non-invasive neuromodulatory technique, has shown promising outcomes in treating different neuropsychiatric disorders such as drug addiction, more specifically on drug craving. The aim in the current study...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Human molecular genetics
دوره 15 7 شماره
صفحات -
تاریخ انتشار 2006