Connexion

GENATLAS PHENOTYPE

last update : 30-11-2009

Symbol	RSTS
Location	16p13.3
Name	Rubinstein-Taybi syndrome
Other name(s)	Broad thumbs-hallux syndrome Rubinstein syndrome chromosome 16p13.3 deletion
Corresponding gene	CREBBP
Other symbol(s)	RTS, DEL16P13.3
Main clinical features	distinctive craniofacial features with microcephaly, downslanting palpebral fissures, beaked nose with the columella extending below the nares and highly arched palate broad and often angulated thumbs and great toes, mental retardation, may be associated with congenital heart disease (hypoplastic left heart) and polysplenia
Genetic determination	autosomal dominant
	chromosomal
Prevalence	estimated 1/125 000 livebirths, 50 p100 of RSTS patients (PMID: 19533794)
Related entries	include severe RSTS (MIM 610543)
Function/system disorder	multisystem/generalized
	mental retardation
Type	MCA/MR

Gene product

Name

CREB binding protein (CREBBP) transcriptional coactivator interacting with a number of proteins

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments

deletion		haploinsufficiency	~10 p100 of patients, detected by FISH using 5 cosmid probes spanning the 150 Kb of the CREEBBP gene
missense		abnormal protein/loss of function	mutations that affect only the HAT domain of CBP responsible of loss of HAT activity ( mutation R1664H, N1978S )
abnormal splicing		abnormal protein/loss of function	nonsense, missence and splicing mutations of CREBBP have been described in 35 p100 of patients
	translocation		Some rare patients have apparently balanced translocations or inversions involving 16p13.3
	deletion		submicroscopic deletions in 16p13

Remark(s)

belongs to the group of "chromatin disorders" ; CREBBP mutations in 50 percent of cases

Genotype/Phenotype correlations

severe RSTS ( typical facial and skeletal anomalies, failure to thrive, seizures and intractable infections) is associated with a chr 16p13.3 deletion syndrome encompassing telomeric neighbor genes of CREBBP (TRAP1, DNASE1) (PMID: 16783566))

duplications have a recognizable phenotype, characterized by normal to moderately retarded mental development, normal growth, mild arthrogryposis, frequently small and proximally implanted thumbs and characteristic facial features (PMID: 19833603))