Duplication 16p13.3 and the CREBBP gene: confirmation of the phenotype.
The introduction of molecular karyotyping technologies into the diagnostic work-up of patients with congenital disorders permitted the identification and delineation of novel microdeletion and microduplication syndromes. Interstitial 16p13.3 duplication, encompassing the CREBBP gene, which is mutated or deleted in the Rubinstein-Taybi syndrome, have been proposed to cause a recognisable syndrome with variable intellectual disability, normal growth, mild facial dysmorphism, mild anomalies of the extremities, and occasional findings such as developmental defects of the heart, genitalia, palate or the eyes. We here report the phenotypic and genotypic delineation of 9 patients carrying a submicroscopic 16p13.3 duplication, including the smallest 16p13.3 duplication reported so far. Careful clinical assessment confirms the distinctive clinical phenotype and also defines frequent associated features : marked speech problems, frequent ocular region involvement with upslanting of the eyes, narrow palpebral fissures, ptosis and strabismus, frequent proximal implantation of thumbs, cleft palate/bifid uvula and inguinal hernia. It also confirms that CREBBP is the critical gene involved in the duplication 16p13.3 syndrome.
Département de génétique médicale, CHRU Amiens, France. demeer.benedicte@chu-amiens.fr
Bénédicte
B
Demeer
Joris
J
Andrieux
Aline
A
Receveur
Gilles
G
Morin
Florence
F
Petit
Sophie
S
Julia
Ghislaine
G
Plessis
Dominique
D
Martin-Coignard
Bruno
B
Delobel
Helen V
HV
Firth
Ann C
AC
Thuresson
Sandrine
S
Lanco Dosen
Kerstin
K
Sjörs
Cedric
C
Le Caignec
Koenraad
K
Devriendt
Michèle
M
Mathieu-Dramard
D000293:Adolescent; D050882:CREB-Binding Protein / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D058674:Chromosome Duplication; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D012415:Rubinstein-Taybi Syndrome / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome
D050882:CREB-Binding Protein