Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome

Autor: Menke, L.A., Gardeitchik, T., Hammond, P., Heimdal, K.R., Houge, G., Hufnagel, S.B., Ji, J.L., Johansson, S., Kant, S.G., Kinning, E., Leon, E.L., Newbury-Ecob, R., Paolacci, S., Pfundt, R., Ragge, N.K., Rinne, T., Ruivenkamp, C., Saitta, S.C., Sun, Y., Tartaglia, M., Terhal, P.A., Essen, A.J. van, Vigeland, M.D., Xiao, B., Hennekam, R.C., DDD Study
Přispěvatelé: ARD - Amsterdam Reproduction and Development, General Paediatrics, APH - Quality of Care, Human Genetics
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Models
Anatomic
0301 basic medicine
Microcephaly
Intellectual disability
PHENOTYPE
DISEASE
Ptosis
Missense mutation
P300
Child
Genetics (clinical)
Exome sequencing
Rubinstein-Taybi Syndrome
Genetics
Sanger sequencing
EP300
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
CREBBP
CREB-Binding Protein
Child
Preschool
symbols
Female
medicine.symptom
Adolescent
Genotype
PROTEIN CBP
Biology
genotype-phenotype correlation
CBP
Short stature
03 medical and health sciences
symbols.namesake
Imaging
Three-Dimensional
medicine
Humans
Genetic Predisposition to Disease
Alleles
Genetic Association Studies
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Rubinstein–Taybi syndrome
Facies
Infant
medicine.disease
030104 developmental biology
Mutation
E1A-Associated p300 Protein
exome sequencing
Zdroj: American Journal of Medical Genetics. Part A, 176(4), 862. Wiley-Liss Inc.
American Journal of Medical Genetics. Part A, 176, 4, pp. 862-876
American journal of medical genetics. Part A, 176(4), 862-876. Wiley-Liss Inc.
American Journal of Medical Genetics. Part A, 176, 862-876
American Journal of Medical Genetics Part A, 176(4), 862-876
American Journal of Medical Genetics. Part A, 176(4), 862-876. Wiley
ISSN: 1552-4825
Popis: Contains fulltext : 190439.pdf (Publisher’s version ) (Closed access) In 2016, we described that missense variants in parts of exons 30 and 31 of CREBBP can cause a phenotype that differs from Rubinstein-Taybi syndrome (RSTS). Here we report on another 11 patients with variants in this region of CREBBP (between bp 5,128 and 5,614) and two with variants in the homologous region of EP300. None of the patients show characteristics typical for RSTS. The variants were detected by exome sequencing using a panel for intellectual disability in all but one individual, in whom Sanger sequencing was performed upon clinical recognition of the entity. The main characteristics of the patients are developmental delay (90%), autistic behavior (65%), short stature (42%), and microcephaly (43%). Medical problems include feeding problems (75%), vision (50%), and hearing (54%) impairments, recurrent upper airway infections (42%), and epilepsy (21%). Major malformations are less common except for cryptorchidism (46% of males), and cerebral anomalies (70%). Individuals with variants between bp 5,595 and 5,614 of CREBBP show a specific phenotype (ptosis, telecanthi, short and upslanted palpebral fissures, depressed nasal ridge, short nose, anteverted nares, short columella, and long philtrum). 3D face shape demonstrated resemblance to individuals with a duplication of 16p13.3 (the region that includes CREBBP), possibly indicating a gain of function. The other affected individuals show a less specific phenotype. We conclude that there is now more firm evidence that variants in these specific regions of CREBBP and EP300 result in a phenotype that differs from RSTS, and that this phenotype may be heterogeneous.
Databáze: OpenAIRE
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