Clinical description and mutational profile of a moroccan series of patients with rubinstein taybi syndrome

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

Cancer du sein chez la femme jeune de moins de 35 ans : à propos de 241 cas.

Ce travail est une étude rétrospective portant sur 241 cas de patientes âgées de 35 ans ou moins et admises pour prise en charge à l’institut national d’Oncologie de Rabat, entre Janvier 2008 et Décembre 2010. L’objectif de l’étude était d’analyser les caractéristiques épidémiologiques, cliniques, histologiques et thérapeutiques du cancer du sein chez la femme jeune et leur influence sur la survie. L’étude des données a trouvé un pic de fréquence chez la tranche d’âge ˃ 30 ans (69.30%), une prédominance de la pauci et nulliparité (80.3%) et la présence d’une forme symptomatique chez toutes les patientes. Histologiquement, il y avait une nette prédominance du CCI (90.3%), des grades SBR II et III (97%). Sur le plan thérapeutique la chirurgie radicale était l’intervention la plus pratiquée (71.40%). La CMT néoadjuvante a été administrée à 20.7% des patientes et l’adjuvante à 75.9%. Le protocole le plus utilisé était celui à base d’anthracyclines (57%). 67.2% des patientes ont bénéficié d’une radiothérapie et 61.6% des patientes avec des récepteurs hormonaux positifs ont reçu une hormonothérapie. Les taux de survie sans rechute et de survie globale à 3 ans étaient de 67.5% et 83.1% respectivement. Ils étaient influencés par le stade tumorale, les signes inflammatoires, le statut ganglionnaire, le grade SBR, les récepteurs hormonaux, le statut triple négatif et l’hormonothérapie. Les conclusions des auteurs sont divergentes mais plaident plutôt en faveur de formes plus évoluées et de pronostic plus défavorable que chez les femmes plus âgées, d’où la nécessité de multiplier les essais cliniques dans le but d’améliorer la survie

A novel frameshift mutation in the XPC gene in a Moroccan patient: a case report

Abstract Background Xeroderma pigmentosum is an autosomal recessive inherited disease. The diagnosis is essentially based on clinical findings and the family history. This genodermatosis is genetically heterogeneous; to date, nine genes have been associated to this disorder. Based on the result of many studies, xeroderma pigmentosum complementation group C is the most common form of xeroderma pigmentosum. A founder mutation in the XPC gene was reported in the Maghreb region of northern Africa. According to these findings, the Department of Medical Genetics in Rabat offers molecular diagnosis by screening for the recurrent mutation c.1643_1644delTG which represents 74% of all the probands with xeroderma pigmentosum. Case presentation We describe the case of a 21-year-old Moroccan son of consanguineous parents diagnosed with xeroderma pigmentosum on the basis of sun-exposed skin abnormalities and bilateral ocular involvement. A molecular study led to the identification of a new frameshift insertion of four nucleotides in exon 9. Conclusions To the best of our knowledge, this mutation has not been described. The sequencing of the ninth exon should be proposed as first line molecular analysis for all Moroccan patients with xeroderma pigmentosum

Surprisingly good outcome in antenatal diagnosis of severe hydrocephalus related to CCDC88C deficiency

Non-syndromic congenital hydrocephalus is aetiologically diverse and while a genetic cause is frequently suspected, it often cannot be confirmed. The most common genetic cause is L1CAM-related X-linked hydrocephalus and that explains only 5%-10% of all male cases. This underlines a current limitation in our understanding of the genetic burden of non-syndromic congenital hydrocephalus, especially for those cases with likely autosomal recessive inheritance. Additionally, the prognosis for most cases of severe congenital hydrocephalus is poor, with most of the surviving infants displaying significant intellectual impairment despite surgical intervention. It is for this reason that couples with an antenatal diagnosis of severe hydrocephalus are given the option, and may opt, for termination of the pregnancy. We present two families with CCDC88C-related recessive congenital hydrocephalus with children who had severe hydrocephalus. Those individuals who were shunted within the first few weeks of life, who did not require multiple surgical revisions, and who had a more distal truncating variant of the CCDC88C gene met their early childhood developmental milestones in some cases. This suggests that children with CCDC88C-related autosomal recessive hydrocephalus can have normal developmental outcomes under certain circumstances. We recommend CCDC88C analysis in cases of severe non-syndromic congenital hydrocephalus, especially when aqueduct stenosis with or without a medial diverticulum is seen, in order to aid prognosis discussion