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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Intelligence Quotient Variability in Klinefelter Syndrome Is Associated With GTPBP6 Expression Under Regulation of X-Chromosome Inactivation Pattern

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Simonetti, Luciane [1] ; Ferreira, Lucas G. A. [2, 1] ; Vidi, Angela Cristina [2, 1] ; de Souza, Janaina Sena [1] ; Kunii, Ilda S. [1] ; Melaragno, Maria Isabel [3] ; de Mello, Claudia Berlim [4] ; Carvalheira, Gianna [3] ; Dias da Silva, Magnus R. [2, 1]
Total Authors: 9
[1] Univ Fed Sao Paulo, Dept Med, Escola Paulista Med, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Biochem, Escola Paulista Med, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Morphol & Genet, Escola Paulista Med, Sao Paulo - Brazil
[4] Univ Fed Sao Paulo, Dept Psychobiol, Escola Paulista Med, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: FRONTIERS IN GENETICS; v. 12, SEP 20 2021.
Web of Science Citations: 0

Klinefelter syndrome (KS) displays a broad dysmorphological, endocrinological, and neuropsychological clinical spectrum. We hypothesized that the neurocognitive dysfunction present in KS relies on an imbalance in X-chromosome gene expression. Thus, the X-chromosome inactivation (XCI) pattern and neurocognitive X-linked gene expression were tested and correlated with intelligence quotient (IQ) scores. We evaluated 11 KS patients by (a) IQ assessment, (b) analyzing the XCI patterns using both HUMARA and ZDHHC15 gene assays, and (c) blood RT-qPCR to investigate seven X-linked genes related to neurocognitive development (GTPBP6, EIF2S3, ITM2A, HUWE1, KDM5C, GDI1, and VAMP7) and XIST in comparison with 14 (male and female) controls. Considering IQ 80 as the standard minimum reference, we verified that the variability in IQ scores in KS patients seemed to be associated with the XCI pattern. Seven individuals in the KS group presented a random X-inactivation (RXI) and lower average IQ than the four individuals who presented a skewed X-inactivation (SXI) pattern. The evaluation of gene expression showed higher GTPBP6 expression in KS patients with RXI than in controls (p = 0.0059). Interestingly, the expression of GTPBP6 in KS patients with SXI did not differ from that observed in controls. Therefore, our data suggest for the first time that GTPBP6 expression is negatively associated with full-scale IQ under the regulation of the type of XCI pattern. The SXI pattern may regulate GTPBP6 expression, thereby dampening the impairment in cognitive performance and playing a role in intelligence variability in individuals with KS, which warrants further mechanistic investigations.</p> (AU)

FAPESP's process: 17/07053-3 - Effect of thyroid hormone on the brain of 3xTg-AD mice, model of Alzheimer's Disease, on glucose and cholesterol metabolism
Grantee:Janaína Sena de Souza
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 18/22763-0 - Ancient DNA, bioengineering and brain "organoids": study of thyroid hormone homeostasis and Alzheimer's Disease markers in NOVA1 gene CRISPR edited stem cells
Grantee:Janaína Sena de Souza
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 21/00684-3 - Next-generation sequencing and functional evaluation of genetic variants in individuals with DDS 46,XX testicular/ ovotesticular SRY-negative
Grantee:Magnus Régios Dias da Silva
Support Opportunities: Regular Research Grants
Grantee:Guiomar Nascimento Gomes
Support Opportunities: Regular Research Grants