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

TYPE AND COUNTER-TYPE FROM SPECIFIC CHROMOSOMAL REGIONS

Several studies have shown the importance of segmental deletions/duplications in the field of chromosome pathologies. Non allelic homologous recombination, NAHR, between chromosomes or sister chromatids, mediated by segmental duplications, is the foundation of frequent mechanisms for structural chromosome mutations such as micro-deletions, micro-duplications, translocations, inversions, and marker chromosomes. We analyzed three distinct genomic regions (22q11.2, 17p11.2, 16p11.2) and we discussed how the same chromosome region can be affected by deletion or by reciprocal duplication, respectively responsible for a syndrome or for a reciprocal counter-syndrome, with different phenotypic manifestation

PTEN hamartoma tumor syndromes in childhood: description of two cases and a proposal for follow-up protocol

PTEN hamartoma tumor syndromes (PHTS) are a spectrum of hamartomatous overgrowth syndromes associated with germline mutations in the tumor suppressor PTEN gene located on 10q23.3. It is widely accepted that two of these disorders,Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome, are allelic conditions. BecausePTENmutations are not identifiable in every case of the PHTS phenotype, the inability to detect a mutation within thePTENgene does not invalidate the clinical diagnosis of Cowden syndrome, or Bannayan–Riley–Ruvalcaba syndrome, in patients who meet diagnostic criteria for these disorders. PTEN mutations are associated with an increased risk for developing breast, thyroid, endometrial, and sometimes renal cancers. Thus, cancer surveillance is the cornerstone of PHTS patient management. Although a consensus cancer surveillance protocol has not been formally instituted, all PTEN mutation carriers should adopt the cancer surveillance strategies proposed for patients with Cowden syndrome. In addition, because gastrointestinal and vascular complications can be more severe in Bannayan– Riley–Ruvalcaba syndrome than in Cowden syndrome, patients with Bannayan–Riley–Ruvalcaba syndrome should be monitored from this point of view too. In this study, we report on two cases with Bannayan–Riley–Ruvalcaba phenotype that showed two different PTEN mutations.Wealso propose practice recommendations for management of PHTS patient