Biomedical subjects

Gevork N Mnatzakanian

Publications and source records attributed to Gevork N Mnatzakanian.

3 recordsLinked to original sources

PubMed2007

Sequence variants within exon 1 of MECP2 occur in females with mental retardation.

A new splice variant of the Rett syndrome gene, MECP2, was recently identified, that includes coding sequence from exon 1, and is the predominant transcript in the central nervous system. This sequence encodes polyalanine and polyglycine stretches within the N-terminal portion of MeCP2, and may confer novel functional properties to the protein. We screened autism, mental retardation (MR), and control populations for sequence variation within this region, and identified variation in approximately 1% of MR cases screened (N = 1,410). No variants were identified in the autism sample (N = 401). Most of these variants occur within a trinucleotide repeat region and result in change in number of alanine or glycine residues within the repeat stretches. We suggest some of these variants may be a relatively frequent cause of non-specific MR or developmental delay.

Adult↗

PubMed2005

Clinical stringency greatly improves mutation detection in Rett syndrome.

BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder of girls, caused by mutations in the X-linked MECP2 gene. Worldwide recognition of the RTT clinical phenotype in the early 1980's allowed many cases to be diagnosed, and established RTT as one of the most common mental retardation syndromes in females. The years since then led to a refinement of the phenotype and the recent elaboration of Revised Diagnostic Criteria (RDC). Here, we study the impact of the presence versus the absence of the use of diagnostic criteria from the RDC to make a diagnosis of RTT on MECP2 mutation detection in Canadian patients diagnosed and suspected of having RTT. METHODS: Using dHPLC followed by sequencing in all exons of the MECP2 gene, we compared mutation detection in a historic cohort of 35 patients diagnosed with RTT without the use of specific diagnostic criteria to a separate more recent group of 101 patients included on the basis of strict fulfillment of the RDC. RESULTS: The MECP2 mutation detection rate was much higher in subjects diagnosed using a strict adherence to the RDC (20% vs. 72%). CONCLUSIONS: These results suggest that clinical diagnostic procedures significantly influence the rate of mutation detection in RTT, and more generally emphasize the importance of diagnostic tools in the assessment of neurobehavioral syndromes.

Behavior↗

PubMed2004

A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome.

Rett syndrome is caused by mutations in the gene MECP2 in approximately 80% of affected individuals. We describe a previously unknown MeCP2 isoform. Mutations unique to this isoform and the absence, until now, of identified mutations specific to the previously recognized protein indicate an important role for the newly discovered molecule in the pathogenesis of Rett syndrome.

Base Sequence↗