A paradigmatic autistic phenotype associated with loss of PCDH11Y and NLGN4Y genes

Background: Most studies relative to Y chromosome abnormalities are focused on the sexual developmental disorders. Recently, a few studies suggest that some genes located on Y chromosome may be related to different neurodevelopment disorders. Case presentation: We report a child with sexual developmental disorder associated with a peculiar phenotype characterized by severe language impairment and autistic behaviour associated with a mosaicism [45,X(11)/46,XY(89)] and a partial deletion of the short and long arm of Y chromosome (del Yp11.31q11.23) that also involves the loss of both PCDH11Y and NLGN4Y genes. To our knowledge no study has ever reported the occurrence of the lack of both PCDH11Y and NLGN4Y located in the Y chromosome in the same patient. Conclusions: We hypothesized a functional complementary role of PCDH11Y and NLGN4Y within formation/maturation of the cerebral cortex. The impairment of early language development may be mainly related to the lack of PCDH11Y that underlies the early language network development and the later appearance of the autistic behaviour may be mainly related to deficit of inhibitory glicinergic neurotransmission NLGN4Y-linked

Commonalities and distinctions between two neurodevelopmental disorder subtypes associated with SCN2A and SCN8A variants and literature review

This study was aimed to analyze the commonalities and distinctions of voltage-gated sodium channels, Nav1.2, Nav1.6, in neurodevelopmental disorders. An observational study was performed including two patients with neurodevelopmental disorders. The demographic, electroclinical, genetic, and neuropsychological characteristics were analyzed and compared with each other and then with the subjects carrying the same genetic variants reported in the literature. The clinical features of one of them argued for autism spectrum disorder and developmental delay, the other for intellectual disability, diagnoses confirmed by the neuropsychological assessment. The first patient was a carrier of SCN2A (p.R379H) variant while the second was carrier of SCN8A (p.E936K) variant, both involving the pore loop of the two channels. The results of this study suggest that the neurodevelopmental disorders without overt epilepsy of both patients can be the consequences of loss of function of Nav1.2/Nav1.6 channels. Notably, the SCN2A variant, with an earlier expression timing in brain development, resulted in a more severe phenotype as autism spectrum disorder and developmental delay, while the SCN8A variant, with a later expression timing, resulted in a less severe phenotype as intellectual disability

Le teck javanais : de l’exploitation illégale au boycott dramatique

Planté depuis de nombreux siècles à Java, le teck y a été particulièrement développé au XIXème siècle. Les 200 000 ha de plantation de teck à Java constituent la plus grande plantation de cette essence au monde. Cette ressource est néanmoins surexploitée, et des ONG mettent en question sa gestion par l’Etat. Il s’agit d’un bois profondément ancré dans la culture Javanaise, dont l’industrie à une longue histoire, mais qui a en quelques années, après la crise asiatique, a vu une flambée des exportations, puis un effondrement des prix à l’exportation. La filière meuble en particulier, est organisée en deux filières parallèles. La première, artisanale, est très liée à l’énorme consommation locale, et entraÓne une forte tension sur les pris locaux, et est en compétition pour l’accès à la ressource avec la seconde, industrielle, qui approvisionne en particulier les marchés étrangers. Face aux problèmes complexes qui se posent, sont proposées des solutions simplistes. La campagne européenne des ONG pour l’embargo sur le teck Indonésien, sensé le Protéger, à des effets pervers et est un remède pire que le mal. L’engagement éthique des grands producteurs, des incitations pour les petits acteurs locaux, et la progressivité des améliorations du système de production paraissent plus raisonnables.

Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response

Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU) activity. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines. We planned to perform the whole TS gene structure by means of sequencing techniques in human colorectal cancer (CRC) samples to try to identify the presence of any possible TS variant form that could be responsible of fluoropyrimidines drug resistance and of the worse prognosis. We performed the TS-DNA gene sequence in 68 CRC from patients of A, B, and C Dukes' stages and different histological grade, but we did not find any mutation in the TS-DNA structure. In the future we intend to widen the TS structure analysis to the metastatic CRCs, because due to their higher genomic instability, they could present a TS variant form responsible of the fluoropyrimidines drug resistance and the worse prognosis

Variable phenotype in 17q12 microdeletions: Clinical and molecular characterization of a new case

Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutations of this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinary alterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer\u2013Rokitansky\u2013 K\ufcster\u2013Hauser Syndrome (MRKH, OMIM277000) in females and, recently,were associatedwith intellectual disability, autistic features, cerebral anomaly and facial dysmorphisms. In this report, we describe a boywith a deletion in 17q12 region detected by SNP array, encompassing the HNF1B gene, that showed dysmorphic features, intellectual disability (ID), serious speech delay and autistic features. In addition, obesity was observed. In order to study the parental origin of the rearrangement, we analyzed selected SNPs in the deleted area in the patient and his parents, showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of maternal origin. Our case confirms the incomplete penetrance and variable expressivity of this deletion, its complex clinical variability, and strengthens the evidence that ID and stereotyped behaviors may be part of the phenotypic spectrum characterizing the affected patients. Also, it is useful to further delineate the phenotypes associated to the deletion being the first case in which obesity has been documented. We present a genotype\u2013phenotype correlation discussing the possible role of some genes, encompassed by the deletion, in the etiology of the observed phenotypes