[Linkage analysis of six Algerian families with autosomal recessive non specific mental retardation]

Mental retardation is one of the most frequent major handicap, with a 1-3% frequency in the general population. The recent progress of molecular biology and cytogenetic allowed to identify new genes for non syndromic autosomal recessive mental retardation. To seek a genetic linkage to the loci implied in the nonspecific mental retardation transmitted into autosomal recessive [ARNSMR] in Algerian families with several affected members and to make the Genetic analysis of ARNSMR for 4 known loci: 3p25-pter; 4q24- q25, 19p13.12 and 1p21.1-p13. The study concerned 34 individuals including 15 patients, belonging to six consanguineous Algerian families. Genotyping was made using polymorphic microsatellite markers and the analysis carried out thanks to the program Gene Mapper software. Statistical analyses were validated using the Fast Link programme of the Easy linkage software [V4:00 betas]. The study carried out made it possible to exclude linkage of all loci for 3 families, nevertheless the linkage of one family to the locus 1p21.1-p13.3 remains possible. The absence of linkage of 4 Algerian families with autosomal recessive mental retardation to 3 well known loci, confirms the genetic heterogeneity of mental retardation. We have to pursue research of candidate genes by whole genome scan

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

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]. Genetic analysis of NSAR-MR: the GRIK2 gene [6q16.3-q21] and the TUSC3 gene [8p22]. Four Tunisian families with NSAR-MR were included in this study. Genotyping was made using polymorphic microsatellite markers and statistical analysis was validated using the Fast Link programme of the Easy linkage software [V4:00beta]. Genotyping and linkage analysis excluded linkage of the GRIK2 gene and TUSC3 gene. Our results confirm the extreme genetic heterogeneity of NSAR-MR

[Pallister-Killian syndrome with additional manifestations of cleft palate and sacral appendage]

Report of a rare congenital abnormalities. We report a rare case of Pallister-Killian syndrome in a 33 weeks gestation infant. In addition to the characteristic phenotype, this patient had a cleft palate, diaphragmatic hernia and sacral appendage. These additional manifestations are not among the Pallister-Killian syndrome's features. The diagnosis was made in antenatal period by cytogenetic studies and showed mosaic 47, XY +I [12p]. Presence of diaphragmatic hernia makes this syndrome, prenatally letal, similar to the Fryns syndrome and then requires skin biopsy and fiboblast chromosome examination for cytogenetic diagnosis

X linked mental retardation

Mental retardation [MR] is a group of heterogeneous clinical conditions. There are more than 900 genetic disorders associated with MR and it affects around 3%of the general population. Many MR conditions described are syndromic, fragile X syndrome being the most common clinical entity among them. Xlinked mental retardation [XLMR] is subdivided in two categories: syndromic XLMR [MRXS] when MR is associated with clinical features and non-syndromic XLMR [MRX] when MR is isolated. The aim of this systematic review of the literature was to join together the results of several studies related to X linked mental retardation and to present various genes implicated in this disease. In this review, focus has been given on genes implicated in mental retardation, the clinical data and on phenotype-genotype correlations. An exhaustive electronic and library research of the recent literature was carried out on the Web sites "Science Direct" and "Interscience Wiley". The key words used were "mental retardation", "X chromosome", "gene", "syndromic mental retardation", "non-syndromic mental retardation". In this review a number of X linked genes, the clinical features associated with the gene abnormality, and the prevalence of the disease gene are discussed. We classified these genes by order of their first implication in MR. A table presented on the XLMR Update Web site who list the 82 known XLMR genes is available as XLMR Genes and corresponding proteins

[First trimester ultrasound: an early screening tool for fetal structural and chromosomic abnormalities]

Prenatal diagnosis has been greatly expanded in recent years. Many biological and sonographic criteria participated in the development of fetal medicine. Analyze the contribution of first trimester ultrasound in prenatal diagnosis of aneuploidy and early fetal malformations, and its impact on the strategy of prevention of disability. A prospective longitudinal descriptive study including all women who did a first trimester ultrasound during their pregnancy. We evaluated the detection rate of malformations and chromosomal abnormalities of the morphological embryonary study and nuchal translucency. These tests were then confronted with the results of fetal samples and the outcome of pregnancy. 593 ultrasound examinations were performed. The average age of pregnant women was 32.7 years. The mini-morphological ultrasound study revealed 26 abnormalities [3 major lethal malformations, 5 cystic hygroma and 18 increased nuchal translucency]. Chromosomal abnormalities were found in six cases. The first trimester ultrasound has ensured the detection of 2/3 of total aneuploidies of the study. The first trimester ultrasound allows early detection of a large number of aneuploidies and fetal malformations

[Molecular diagnosis of fragile X syndrome]

The fragile X syndrome was the most frequent etiology of hereditary mental retardation but the clinical diagnosis is not easy and the indivivual clinical symptoms were not specific so the confirmation will be made par molecular study of the gene of the fragile X syndrome. of our study is to realise the molecular diagnosis of the fragile X syndrome in 200 Tunisian boys with mental retardation. Shows that the frequency of the fragile X syndrome is 7.6%. In the most cases there is a family history of mental retardation with midium age at 11 years. All the boys with the full mutation have mental retardation, dysmorphic features and macro-orchidism [pubescent boy]. The screening of the molecular abnormalitie of FMRI gene must be realised in every boy with mental retardation or boy with delayed speach without any identified etliology. The earlier diagosis is important-for genetic counselling

[Interest of studying subtelomeric abnormalities by in situ fluorescent hybridization to explore idiopathic mental retardation]

Nowadays, the genetic basis of mental retardation is a huge field of investigations. Genetic abnormalities frequently give rise to a mental retardation phenotype and are observed in 10 to 40% of known etiologies. New syndromes have identified [chromosome 1p, 22q, 3q29 and 9q34] but for 60% of patients there is no etiology because there is no characteristic phenotype. Many studies involve subtelomeric duplications and deletions in idiopathic mental retardation. The auteurs describe and discuss the interest and the limits of telomeric FISH [Chromoprobe Multiprobe T System] in exploring mental retardation

Autism: an overview of genetic aetiology

Autism is a pervasive developmental disorder characterised by impairment in social interaction and in communication, with unusual behaviour. Genetic factors are predominant in autism pathogenesis. Interactions between multiple genes cause [idiopathic] autism but epigenetic factors and exposure to environmental modifiers may contribute to variable expression of autism-related traits. The genetic polymorphism and the phenotypic heterogeneity make the autism a complex disorder to study. Genetic research on families with multiple affected children and biochemical mechanisms studies represent the sources for identifying the susceptibility genes in autism. Children with dysmorphic features, congenital anomalies, mental retardation, or family members with developmental disorders are those most likely to benefit from extensive medical testing and genetic consultation

[Treacher collins syndrome: clinical and genetic aspects about 4 cases]

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 1 in 50.000 live births, which includes facial and auricular anomalies leading to functional, morphological and psychological difficulties due to related handicaps. Treacher Collins syndrome is inherited as autosomal dominant pattern with a variable expressivity and incomplete penetrance of "TCOF1" gene localized at incomplete penetrance of "TCOF1" gene localized at 5q31.3q32. Today the gene is well identified and several mutations have been reported. In this paper we report the case of 4 Tunisian unrelated girls with Treacher Collins syndrome. One of them was born from an affected father. Clinical diagnostic was performed between age 12 days and 2 years demonstrating the large dysmorphic expression. Main clinical features were present in all reported cases. Family at risk might have genetic counselling and probably prenatal diagnostic in some situations. Out of our observations, we gave genetic counselling and proposed ultrasound prenatal diagnosis for two families without molecular study

[Molecular analysis of the smni and naip genes in 60 Tunisian spinal muscular atrophy patients]

In this study we examined the deletion of SMN and NAIP genes in 60 Tunisian families There were 35 patients with type I SMA. 18 with type II SMA, 6 with type Ill SMA and 1 with type IV SMA .The age of onset was before 6 months for type I, between 6 months and 2 years for type II. between 2 years and 17 years for type III and 30 years for type IV. Exon 7 of SMN 1 gene was homozygously deleted in 95% [57/60] of SMA patients. There was a higher frequency of homozygous absence of SMN I in type I and type 11 [100% and 94% respectively] than in type III [66,7%]. SMN 1 exon 8 was undetectable in 88%[53/60] of patients .The case type II patient with homozygous deletion of SMN I exon 7 and not exon 8 was tested for the presence of a hybrid SMN gene. This patient showed in the second PCR a SMN I exon 8 product by restriction site assay indicating that a gene conversion event had occurred. All parents' individuals retained one copy of their SMN I gene. Exon 5 of NAIP gene was homozygously deleted in 58% [35/60] of patients [77% in type I [27/35], 27, 7% in type 11 [5/18], 50% [3/6] in type III [Table 1]. No patient had a deletion in NAIP gene without a deletion in the SMN1 gene. Homozygous deletion of NAIP exon 5 was detected in 1 parent. Our results show that the incidence of NAIP deletion is higher in the more severe SMA cases

Genetique des maladies inflammatoires cryptogenetiques de l'intestin

The inflammatory bowel disease [IBD] are multifactorial diseases involving the interaction of genetic and environmental factors. In genetic terms, the IBD are polygenic and multigenic disorders with incomplete penetrance. In the late decade, investigators have applied the complementary techniques of genome-wide scanning and candidate gene analysis to search susceptibility genes. The IBD susceptibility regions, widely replicated, are in chromosomes 16 [IBD1], 12 [IBD2] and 6 [IBD3]. Recently, a signification have been reported with crohn's disease and NOD2/ CARD15 gene. This gene is an appropriate candidate gene because its localization and function. More studies is necessary to confirm this association, search an other variants of this gene and other candidate gene. This studies provide best comprehension of the disease pathogenesis and deliver clinical application

Etude epidemiologique et genetique de la trisomie 21 entunisie

Trisomy 21 is the most common non lethal chromosomal anomaly. The authors give study's results of 500 cases, realised in genetic clinics [Charles Nicolle Hospital, Tunis]. This sutdy showed male frequency [54.6%] the fourth birth rate is present in 40.6% of the patietns, the mean maternal age is 32 years and 36% of patients are born from mothers over 35 years. Consanguinity has no effect. Dysmorphy is observed with great v…riation in all cases. Cytogenetic analysis showed homogeneous free trisomy 21 in 91.2% cases, masochism in 4.8% and translocation in 4% correlation between clinical and cytogenetic study showed high incidence of Dysmorphy and malformation in transcolated trisomy 21. Moreover psychmotor development is related to genetic first advising age and to cytogenetic imbalance