Clinical description and mutational profile of a Moroccan series of patients with Rubinstein Taybi syndrome

Abstract

Background: Rubinstein-Taybi syndrome (RSTS; OMIM 180849) is a rare autosomal dominant developmental disorder with an estimated prevalence of one case per 125,000 live births. RSTS is characterized by typical face, broad thumbs and halluces, short stature, and intellectual disability. Facial dysmorphy is characteristic with microcephaly, low frontal hairline, arched eyebrows, long eyelashes, convex profile of nose, narrow palate, and micrognathia. RSTS is mainly due to mutations or microdeletions of the CREBBP gene (about 60%) and more rarely of the EP300 gene (8%).
 Objective: Clinical description and identification of mutations of patients with Rubinstein Taybi syndrome.
 Methods: PCR and direct sequencing of CREBBP gene.
 Results: We report here, the clinical and molecular data of a series of six Moroccan patients with a phenotype of RSTS. The molecular study of the major gene CREBBP (by Sanger Sequencing followed by CGH array, if sequence normal) revealed point mutations in five patients. For the sixth patient, CGH array revealed a microdeletion carrying the CREBBP gene. Through this work, we emphasize the importance of clinical expertise in the diagnosis, management and genetic counseling in Rubinstein Taybi syndrome.
 Keywords: Rubinstein Taybi syndrome; CREBBP gene; mutation; Moroccan.

Correlations between phenotype and gene region-specific episignatures in Rubinstein-Taybi syndrome and Menke-Hennekam syndrome

“…Floating-Harbor syndrome (12,14). This might be due to the frameshift or nonsense variants that would escape NMD and cause effects other than merely loss of CREBBP function (15).…”

“…To comprehensively evaluate phenotype similarities and differences, we further collected clinical information from our patients and literatures published previously (3,(7)(8)(9)(10)(11)(12)(13)(14)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). In total, 37 MKHK and 151 RSTS patients (including 115 classical RSTS and 36 patients with non-NMD variants) were enrolled (Table 2).…”

“…However, although different types and locations of pathogenic variants with CREBBP causing two distinct ID syndromes have been clari ed, the heterogenous or atypical phenotypes in RSTS and MKHK still need to be elucidated. For instance, a patient carrying NM_004380.3:c.6169C T (p.Gln2057*) variant was found atypical from the classical RSTS (broad thumbs or big toes, hirsutism) but resembled Floating-Harbor syndrome (12). Other studies also mentioned misleading initial diagnosis in RSTS patients with pathogenic variants located at the last part of CREBBP (13,14).…”

Editorial: Infectious diseases and NCDs persist despite concerted effort

“…The effect of call reminders, short message services (SMS) reminders, and SMS immunization facts on childhood routine vaccination timing and completion in Nigeria 56 reminds us of the potential for innovative technology in the health sector in Africa. We end this reflection on the June 2021 issue of African Health Sciences on a high note: the ‘clinical description and mutational profile of a Moroccan series of patients with Rubinstein Taybi syndrome.’ 57 .…”