Molecular autopsy and clinical family screening in a case of sudden cardiac death reveals ACTN2 mutation related to hypertrophic/dilated cardiomyopathy and a novel LZTR1 variant associated with Noonan syndrome.

Background: Genetic cardiac diseases are the main trigger of sudden cardiac death (SCD) in young adults. Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiomyopathy and accounts for 0.5 to 1% of SCD cases per year.

Novel Mutation in the First Tunisian Family With Warburg Micro Syndrome.

Background And Purpose: Warburg Micro syndrome (WARBM) is a rare autosomal recessive genetic disease characterized by ocular, neurologic, and endocrine anomalies. WARBM is a phenotypically and genetically heterogeneous syndrome caused by mutations in , , , and . Here we present the clinical and genetic characterization of a consanguineous Tunisian family with a WARBM phenotype presenting two pathogenic variations, one of which is on .

3M syndrome: A Tunisian seven-cases series.

3M syndrome (3MS) is a rare autosomal recessive primordial growth disorder characterized by a severe pre- and post-natal growth deficiency, minor dysmorphisms and skeletal abnormalities, contrasting with normal intellect and endocrine function. Three different genes have been so far involved in the disease, with mutations in CUL7, OBSL1 and CCDC8. The CUL7 gene mutations are accountable for 77,5% of the genetically confirmed patients, with a founder mutation identified in exon 24 for the Maghreb families.

Spectrum of Genetic Diseases in Tunisia: Current Situation and Main Milestones Achieved.

Genetic diseases in Tunisia are a real public health problem given their chronicity and the lack of knowledge concerning their prevalence and etiology, and the high rates of consanguinity. Hence, we performed systematic reviews of the literature in order to provide a more recent spectrum of these disorders and to expose the challenges that still exist to tackle these kinds of diseases. A manual textual data mining was conducted using MeSH and PubMed databases.

Identification of two additional novel mutations in the AR gene associated with severe forms of androgen insensitivity syndrome.

The Androgen insensitivity syndrome (AIS) in its complete form (CAIS) is a disorder in abnormal male development characterized by a complete female phenotype in a 46,XY individual. The most frequent cause of this disorder is a hemizygous mutation in androgen receptor (AR) gene located in X chromosome. The first aim of this study was to confirm the clinical diagnosis in a series of Tunisian patients with a typical phenotype of CAIS by molecular genetic analysis.

WDR73-related galloway mowat syndrome with collapsing glomerulopathy.

Galloway-Mowat syndrome (GAMOS [MIM 251300]) is a rare autosomal recessive disorder that manifests as a combination of nephrotic syndrome, brain abnormalities and developmental delay. It is a clinically and genetically heterogeneous disease. The WDR73 variations are associated with GAMOS1.

TOP3B: A Novel Candidate Gene in Juvenile Myoclonic Epilepsy?

Juvenile myoclonic epilepsy (JME) is characterized by seizures, severe cognitive abnormalities, and behavior impairments. These features could evolve over time and get worse, especially when the encephalopathy is pharmacoresistant. Thus, genetic studies should provide a better understanding of infantile epilepsy syndromes.

Novel PAX3 mutations causing Waardenburg syndrome type 1 in Tunisian patients.

Waardenburg syndrome (WS) is an auditory-pigmentary disease characterized by a clinical and genetic variability. WS is classified into four types depending on the presence or absence of additional symptoms: WS1, WS2, WS3 and WS4. Type 1 and 3 are mostly caused by PAX3 mutations, while type 2 and type 4 are genetically heterogeneous.

Functional Analysis of Mutations at Codon 127 of the SRY Gene Associated with 46,XY Complete Gonadal Dysgenesis.

Complete gonadal dysgenesis (CGD) is characterized by an incomplete differentiation of the genital organs in a patient with a 46,XY karyotype. It is induced by mutations in the sex-determining region Y (SRY) gene which plays a key role in testis-determining pathways. The aim of this study was to investigate the possible pathogenic nature of a novel SRY mutation (p.

Distinctive findings in a boy with Simpson-Golabi-Behmel syndrome.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked condition characterized by pre and post natal overgrowth, facial malformations, and visceral, skeletal, and neurological anomalies. The physical characteristics of SGBS have been well documented; however there is a lack of description regarding the behavioral phenotype. We report the case of a 6-year-old boy, with confirmed deletion of 6-8 exons of the glypican-3 gene (GPC3) who presents three distinctive findings: the persistence of the craniopharyngeal canal, an immune-allergic specificity, and a scarcely behavioral phenotype consisting in the association of Austim Spectrum Disorder with accompanying mild intellectual disability and language impairments.

RGS6: a novel gene associated with congenital cataract, mental retardation, and microcephaly in a Tunisian family.

Purpose: The object of this study is to identify the underlying genetic defect in a consanguineous Tunisian family affected with autosomal recessive congenital cataract associated with mental retardation and microcephaly.

Methods: A whole-genome scan was performed with polymorphic microsatellites in the axiom data for the screened members. Homozygous regions were analyzed with integrated Systems Tool for Eye gene Discovery (iSyTE), to identify candidate genes with lens-enriched expression that were potentially associated with cataract.

GJB2 and GJB6 screening in Tunisian patients with autosomal recessive deafness.

Unlabelled: Autosomal recessive nonsyndromic deafness (ARNSD or DFNB) is a very common genetically heterogenous disorder. Although DFNB1 mutations are known to be the most frequent cause of this disorder, they are largely dependent on ethnic groups. The aims of our study are to specify the prevalence and the spectrum of GJB2 mutations as well as the prevalence of GJB6 large deletion in Tunisian population.

Epidemiologic and clinical characteristics of 458 Tunisian patients with intellectual deficiency and a reconsidered diagnostic strategy.

Intellectual Deficiency (ID) is a common neuropsychiatric disorder whose etiopathogenesis still insufficiently understood. In the last decade, several surveys, assessing epidemiologic, clinical and etiologic parameters of ID, have been performed but none of them is realized in a Tunisian population. In this retrospective survey, we propose to study these parameters, in a Tunisian cohort of 458 patients with constitutional ID, and to assess our diagnostic strategy.

Prevalence of Bardet-Biedl syndrome in Tunisia.

Bardet-Biedl syndrome (BBS, OMIM 209900) is a ciliopathy causing multivisceral abnormalities. This disease is mainly characterized by obesity, post-axial polydactyly, hypogenitalism, intellectual disabilities, pigmentary retinopathy, and renal deficiency. The prevalence of BBS has been estimated in different populations, ranging from 1 in 160,000 in European populations to 1 in 13,000 in Bedouins from Kuwait.

Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation.

Background: To identify the genetic defect associated with autosomal recessive congenital cataract (ARCC), mental retardation (MR) and ARCC, MR and microcephaly present in most patients in four Tunisian consanguineous families.

Methods: We screened four genes implicated in congenital cataract by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Among its three genes PAX6, PITX3 and HSF4 are expressed in human brain and one gene LIM2 encodes for the protein MP20 that interact with the protein galectin-3 expressed in human brain and plays a crucial role in its development.

Hexasomy of the Prader-Willi/Angelman critical region, including the OCA2 gene, in a patient with pigmentary dysplasia: case report.

Derivatives of chromosome 15, often referred to as inv dup(15), represent the most common supernumerary marker chromosome (SMC). SMC(15)s can be classified into two major groups according to their length: small SMC(15) and large ones. Depending on the amount of euchromatin, the carriers may either present with a normal phenotype or with a recognizable syndrome.

Non-syndromic autosomal recessive mental retardation in Tunisian families : exclusion of GRIK2 and TUSC3 genes.

Background: Mental retardation is one of the most frequent major handicap, with a 1-3 % frequency in the general population, it appear a major problem of public health. The recent progress of molecular biology and cytogenetic allowed to identify new genes for non syndromic autosomal recessive mental retardation (NSAR-MR).

Aim: Genetic analysis of NSAR-MR: the GRIK2 gene (6q16.

A novel frame shift mutation in the PQBP1 gene identified in a Tunisian family with X-linked mental retardation.

Mental retardation (MR) is the most frequent cause of serious handicap in children and young adults. Despite recent progress, in most cases the molecular defects underlying this disorder remain unknown. Linkage studies followed by mutational analysis of known X-chromosomal genes related to mental retardation (MRX genes) localized within defined genetic intervals represent a rational strategy to identify a genetic cause of the disorder.

[Molecular diagnosis of fragile X syndrome].

Background: The fragile X syndrome was the most frequent etiology of hereditary mental retardation but the clinical diagnosis is not easy and the individual clinical symptoms were not specific so the confirmation will be made par molecular study of the gene of the fragile X syndrome. The aim of our study is to realise the molecular diagnosis of the fragile X syndrome in 200 Tunisian boys with mental retardation. Our results shows that the frequency of the fragile X syndrome is 7,6%.

Autosomal recessive acro-fronto-facio-nasal dysostosis associated with genitourinary anomalies: a third case report.

We report on a 22-day-old Tunisian boy born to consanguineous (first-cousin) parents (F = 1/16). The patient presents wide forehead with frontal encephalocele, wide anterior fontanel, marked hypertelorism, coloboma of the upper lids, proptosis, congenital glaucoma, broad nose, syndactyly between fingers 3 and 4, hypoplastic 3rd, 4th and 5th toes with nail dysplasia, hypospadias with cleft glans, bifid scrotum. Brain MRI showed right frontal encephalocele with anomalies of the cortical gyration without any corpus callosum abnormality.

[Treacher-Collins syndrome: clinical and genetic aspects apropos of 4 cases of which 1 is familial].

Treacher Collins syndrome was first mentioned by Thompson in 1847, and described by Treacher Collins in 1900, then it was called mandibulo-facial dysostosis and well defined by Franceschetti in 1949. It is a very rare affection occurring lin 50.000 live births, which includes facial and auricular anomalies leading to functional, morphological and psychological difficulties due to related handicaps.