Clinical Trials 2008: Clinical Trials 2008: Genotype/Phenotype Genotype/Phenotype Jeffrey L. Neul M.D., Jeffrey L. Neul M.D., Ph.D. Ph.D. Assistant Professor Assistant Professor Division of Neurology Division of Neurology Department of Pediatrics Department of Pediatrics Assistant Medical Assistant Medical Director Director Blue Bird Circle Rett Blue Bird Circle Rett Center Center
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Clinical Trials 2008: Genotype/Phenotype Jeffrey L. Neul M.D., Ph.D. Assistant Professor Division of Neurology Department of Pediatrics Assistant Medical.
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Jeffrey L. Neul M.D., Ph.D.Jeffrey L. Neul M.D., Ph.D.Assistant ProfessorAssistant Professor
Division of NeurologyDivision of NeurologyDepartment of PediatricsDepartment of Pediatrics
Assistant Medical DirectorAssistant Medical DirectorBlue Bird Circle Rett CenterBlue Bird Circle Rett CenterBaylor College of MedicineBaylor College of Medicine
8 mutations account for 55-65% cases in typical RTT
MECP2
C terminal truncationsaccount for 8-10%
R106WR133C
T158M
R168X
R255X
R270X
R294X
R306Cmissensemissense
truncatingtruncating
Large deletions account for 7-10%
Genotype/phenotype correlation in typical RTTGenotype/phenotype correlation in typical RTT
Goal: Determine if there is any clinical difference Goal: Determine if there is any clinical difference between specific mutationsbetween specific mutations
Large cohort (285 cases) allows analysis Large cohort (285 cases) allows analysis between common specific mutationsbetween common specific mutations
Participants: Girls and Women with Rett Participants: Girls and Women with Rett Syndrome seen at UAB or TCH/BCMSyndrome seen at UAB or TCH/BCM
Exon 1Exon 1 Large DNA rearrangements (deletions)Large DNA rearrangements (deletions)
Neul et al., Neurology 2008; 70: 1313-1321.Neul et al., Neurology 2008; 70: 1313-1321.
Typical Rett Syndrome: Typical Rett Syndrome: Clinical CriteriaClinical Criteria
Normal pre/perinatal periodNormal pre/perinatal period Postnatal deceleration of head growthPostnatal deceleration of head growth Loss of purposeful hand skillsLoss of purposeful hand skills Stereotypic hand movementsStereotypic hand movements Communication dysfunction Communication dysfunction Social withdrawalSocial withdrawal Absence of other disease processesAbsence of other disease processes
Clinical Severity Score-PercyClinical Severity Score-Percy Clinical scoring systemClinical scoring system Rated from 0 (better) to 5 (worse)Rated from 0 (better) to 5 (worse)