Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene.
Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder characterized by postnatal growth deficiency, skeletal abnormalities, dysmorphic features and cognitive deficit. Mutations in two genes, CREBBP and EP300, encoding two homologous transcriptional co-activators, have been identified in ˜55% and ˜3-5% of affected individuals, respectively. To date, only eight EP300-mutated RSTS patients have been described and 12 additional mutations are reported in the database LOVD. In this study, EP300 analysis was performed on 33 CREBBP-negative RSTS patients leading to the identification of six unreported germline EP300 alterations comprising one deletion and five point mutations. All six patients showed a convincing, albeit mild, RSTS phenotype with minor skeletal anomalies, slight cognitive impairment and few major malformations. Beyond the expansion of the RSTS-EP300-mutated cohort, this study indicates that EP300-related RSTS cases occur more frequently than previously thought (˜8% vs 3-5%); furthermore, the characterization of novel EP300 mutations in RSTS patients will enhance the clinical practice and genotype-phenotype correlations.
Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milano, Italy.
G
G
Negri
D
D
Milani
P
P
Colapietro
F
F
Forzano
M
M
Della Monica
D
D
Rusconi
L
L
Consonni
L G
LG
Caffi
P
P
Finelli
G
G
Scarano
C
C
Magnani
A
A
Selicorni
S
S
Spena
L
L
Larizza
C
C
Gervasini
D000293:Adolescent; D000328:Adult; D050882:CREB-Binding Protein / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D050881:E1A-Associated p300 Protein / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D012415:Rubinstein-Taybi Syndrome / Q000235:genetics* / Q000503:physiopathology; D017384:Sequence Deletion
D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
EP300; Rubinstein-Taybi syndrome; exonic deletions; genotype-phenotype correlations; point mutations