In the era of the diseasomes and interactome networks, linking genetics with phenotypic traits in Turner syndrome should be studied thoroughly. As a part of this stratagem, mosaicism of both X and Y chromosome which is a common finding in TS and an evaluation of congenital heart diseases in the different situations of mosaic TS types, can be helpful in the identification of disturbed sex chromosomes, genes and signaling pathway actors. Here we report the case of a mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms and dissections at an early age. The mosaicism included two cell lines, well-defined at the cytogenetic and molecular levels: a cell line which is monosomic for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal genes that are present on the X and Y chromosomes and escape X inactivation: 45,X[8]/46,X,idic(Y)(pter→q11.2::q11.2→pter)[42]. This case generates two hypotheses about the contribution of genes linked to the sex chromosomes and the signaling pathways involving these genes, in left-sided heart diseases. The first hypothesis suggests the interaction between X chromosome and autosomal genes or loci of aortic development, possibly dose-dependent, and which could be in the framework of TGF-β-SMAD signaling pathways. The second implies that left-sided congenital heart lesions involve sex chromosomes loci. The reduced dosage of X chromosome gene(s), escaping X inactivation during development, contributes to this type of CHD. Regarding our case, these X chromosome genes may have homologues at the Y chromosome, but the process of inactivation of the centromeres of the isodicentric Y spreads to the concerned Y chromosome genes. Therefore, this case emerges as an invitation to consider the mosaics of Turner syndrome and to study their phenotypes in correlation with their genotypes to discover the underlying developmental and genetic mechanisms, especially the ones related to sex chromosomes.

No abstract

Background Uridine diphosphate‐glucuronosyl transferase 1A1 ( UGT1A1 ), which is the major UGT1 gene product, is located on chromosome 2q37. The expression of UGT1A1 is relatively managed by a polymorphic dinucleotide repeat inside the promoter TATA box consisting of 5–8 copies of a TA repeat. A (TA) 6TAA is considered as the wild type. The A (TA) 7TAA allele has been identified as the most frequent allele in the Caucasian populations while A (TA) 8TAA allele remains the rarest allele worldwide in North Africa, including the Arab populations. Methods The spectrum of UGT1A1 genetic mutations in seventeen Tunisian children affected by persistent unconjugated hyperbilirubinemias is represented in addition to their relatives, notably parents, sisters, and brothers. Tunisian children, from 16 unrelated families as well as a 17 th family without CN1 affected child, were originated from the West Center of Tunisia. The promoter region and coding exons of the UGT1A1 were PCR amplified, subsequently subjected to Sanger sequencing. Results The frequencies of genotypes in CN1 patients were as follows (TA) (7/7) (12/17: 70.6%) and (TA) (8/8) (5/17: 29.4%). All patients harbored the c.1070A>G mutation of exon 3 ( UGT1A1 *16) in the homozygous state. Among relatives of our patients ( n = 16), who were all heterozygotes for UGT1A1 *16, 13/16 (81.25%) had a heterozygous state for UGT1A1 ∗1/ UGT1A1 ∗28 or (TA) (6/7) and, 18.75% (3/16) were heterozygous for UGT1A1 ∗28/ UGT1A1 ∗37 or (TA) (7/8) of the promoter polymorphisms. Conclusion UGT1A1 *16 accompanied with UGT1A1 *28 or UGT1A1 *37 had a specific geographic and ethnic distribution for CN pathogenesis in this Tunisian cohort.

No abstract

Introduction Age at onset of pediatric bipolar spectrum disorder (BSD) is an important marker of a more severe form and a highly heritable mood/mental disorder. Objectives Here, we report a familial Tunisian BSD follow-up study showing a very early onset of the BSD at the neonatal period. Methods A 28-year-old female and her 30-year old sister were referred for genetic and psychological assessments due to recurrent depressive episodes. Results Psychological assessment revealed a BSD type II with episodes of hypomania for both patients. The 30-year old sister presented a mixed form of BSD coupled with autistic traits, hyposomnia and obsessive-compulsive behaviors. Intellectual and cognitive abilities were without concerns. Familial history revealed BDS among paternal relatives including the brothers’ and sisters’ father as well as all their uncles offspring’s, and their grandparents, who were consanguineous. The depressive mood was a common sign in the three generations. Personal history revealed significant signs of a very early onset of the disorder since the neonatal period for the two sisters as well as for their four paternal cousins who also presented BSD features. Familial risk of BSD in this family correlates with a variably higher personal risk of other psychiatric disorders such as anxiety, drug abuse, personality disorders, and autism spectrum disorder. Conclusions Environmental conditions, familial care and educational level have a strong correlation with the severity and the efficiency of cognitive management of BSD and its psychiatric comorbidities. BSD is highly heterogeneous and polygenic and personalized management has considerable clinical repercussions benefits. Disclosure No significant relationships.