Pseudoautosomal abnormalities in terminal AZFb+c deletions are associated with isochromosomes Yp and may lead to abnormal growth and neuropsychiatric function.

STUDY QUESTION: Are copy number variations (CNVs) in the pseudoautosomal regions (PARs) frequent in subjects with Y-chromosome microdeletions and can they lead to abnormal stature and/or neuropsychiatric disorders? SUMMARY ANSWER: Only subjects diagnosed with azoospermia factor (AZF)b+c deletions spanning to the end of the Y chromosome (i.e. terminal deletions) harbor Y isochromosomes and/or cells 45,X that lead to pseudoautosomal gene CNVs, which were associated with abnormal stature and/or neuropsychiatric disorders. WHAT IS KNOWN ALREADY: The microdeletions in the long arm of the Y chromosome (Yq) that include the loss of one to three AZF regions, referred to as Yq microdeletions, constitute the most important known etiological factor for primary spermatogenic failure. Recently, controversy has arisen about whether Yq microdeletions are associated with gain or loss of PAR genes, which are implicated in skeletal development and neuropsychiatric function. STUDY DESIGN, SIZE, DURATION: We studied a cohort of 42 Chilean patients with complete AZF deletions (4 AZFa, 4 AZFb, 23 AZFc, 11 AZFb+c) from a university medical center, diagnosed over a period of 15 years. The subjects underwent complete medical examinations with special attention to their stature and neuropsychiatric function. PARTICIPANTS/MATERIALS, SETTING, METHODS: All subjects were characterized for Yq breakpoints by PCR, and for CNVs in PARs by multiplex ligation-dependent probe amplification (MLPA), followed by qPCR analysis for genes in PAR1 (SHOX and ZBED1), PAR2 (IL9R) and two single copy genes (SRY and DDX3Y, respectively located in Yp11.3 and AZFa). In addition, karyotypes revision and fluorescence in situ hybridization (FISH) for SRY and centromeric probes for X (DXZ1) and Y (DYZ3) chromosomes were performed in males affected with CNVs. MAIN RESULTS AND THE ROLE OF CHANCE: We did not detect CNVs in any of the 35 AZF-deleted men with interstitial deletions (AZFa, AZFb, AZFc or AZFb+c). However, six of the seven patients with terminal AZFb+c deletions showed CNVs: two patients showed a loss and four patients showed a gain of PAR1 genes, with the expected loss of VAMP-7 in PAR2. In these patients, the Yq breakpoints localized to the palindromes P8, P5 or P4. In the four cases with gain of PAR1, qPCR analysis showed duplicated signals for SRY and DDX3Y and one copy of IL9R, indicating isodicentric Yp chromosomes [idic(Y)] with breakpoint in Yq11.22. The two patients who had loss of PAR1, as shown by MLPA, had an additional reduction for SRY and DDX3Y, as shown by qPCR, associated with a high proportion of 45,X cells, as determined by FISH and karyotype. In agreement with the karyotype analysis, we detected DYZ3++ and DYZ3+ cells by FISH in the six patients, confirming idic(Y) and revealing additional monocentric Y chromosome [i(Y)]. Five patients had a history of major depressive disorders or bipolar disorder, and three had language impairment, whereas two patients showed severe short stature (Z score: -2.75 and -2.62), while a man with bipolar disorder was very tall (Z score: +2.56). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The number of males studied with Y-chromosome microdeletions and normozoospermic controls with normal karyotypes may not be enough to rule out an association between AZF deletions and PAR abnormalities. The prevalence of Y isochromosomes and/or 45,X cells detected in peripheral blood does not necessarily reflect the variations of PAR genes in target tissues. WIDER IMPLICATIONS OF THE FINDINGS: This study shows that CNVs in PARs were present exclusively in patients with terminal AZFb+c deletions associated with the presence of Y isochromosomes and 45,X cells, and may lead to neuropsychiatric and growth disorders. In contrast, we show that men with interstitial Yq microdeletions with normal karyotypes do not have an increased risk of PAR abnormalities and of phenotypical consequences. Moreover, our results highlight the importance of performing molecular studies, which are not considered in the usual screening for patients with Yq microdeletions. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Fund for Scientific and Technological Development of Chile (FONDECYT), grant no. 1120176 (A.C.). The authors declare that no conflicting interests exist.

[Evaluation of the community integration of persons with lateralised post-acute acquired brain injury]. / Valoracion de la integracion en la comunidad de las personas con daño cerebral adquirido postagudo lateralizado.

INTRODUCTION. Hemispheric specialization is a topic of interest that has motivated an enormous amount of research in recent decades. After a unilateral brain injury, the consequences can affect various areas of specialization, leading, depending on the location of the injury, impairment in quality of life and community integration. PATIENTS AND METHODS. Cross-sectional study with a sample of 58 patients, 28 traumatic brain injury (TBI) and 30 cerebrovascular accidents, both lateralized. The level of integration in the community is measured by the Community Integration Questionnaire. RESULTS. There were three groups analyzed by considering unilateral injury (full sample, stroke sample, and TBI sample). Results showed a significantly high community integration of people with right hemisphere injury. However, to measure the level of community integration between TBI and stroke, the results showed no significant differences. CONCLUSION. According to the results of the study people with brain injury in the right hemisphere have a better community integration than people with lesions in the left hemisphere regardless of the origin of the lesions (vascular or traumatic). We discussed the reasons that may motivate the differences and clinical implications.

TITLE: Valoracion de la integracion en la comunidad de las personas con daño cerebral adquirido postagudo lateralizado.Introduccion. La especializacion hemisferica es un tema de interes que ha motivado un gran volumen de investigacion en las ultimas decadas. Tras una lesion cerebral lateralizada, las secuelas pueden afectar a diversas areas de especializacion, provocando, en funcion de la localizacion de la lesion, una afectacion en la calidad de vida y en la integracion comunitaria. Pacientes y metodos. Estudio transversal con una muestra de 58 pacientes, 28 con traumatismos craneoencefalicos (TCE) y 30 con accidentes cerebrovasculares (ACV), ambos lateralizados. El nivel de integracion en la comunidad se midio con el cuestionario de integracion comunitaria (CIQ). Resultados. De los grupos analizados teniendo en cuenta la lesion lateralizada (muestra completa, muestra de ACV y muestra de TCE), los resultados mostraron una significativamente mayor integracion comunitaria de las personas con lesion en el hemisferio derecho. Sin embargo, al medir el nivel de integracion comunitaria entre TCE y ACV, los resultados no mostraron diferencias significativas. Conclusion. Segun los resultados del estudio, las personas con lesion cerebral en el hemisferio derecho presentan una mejor integracion comunitaria que las personas con lesion en el hemisferio izquierdo, con independencia del origen de las lesiones (vascular o traumatica). Se discuten las razones que pueden motivar las diferencias y las implicaciones clinicas.