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.
Gauthier
Julie
J
Department of Biology, McGill University, Montreal, Canada.
de Amorim
Giovana
G
Mnatzakanian
Gevork N
GN
Saunders
Carol
C
Vincent
John B
JB
Toupin
Sylvie
S
Kauffman
David
D
St-Onge
Judith
J
Laurent
Sandra
S
Macleod
Patrick M
PM
Minassian
Berge A
BA
Rouleau
Guy A
GA
D001519:Behavior; D002170:Canada; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis / Q000592:standards*; D005091:Exons / Q000235:genetics; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics*; D015518:Rett Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004247:DNA