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oai:repisalud.isciii.es:20.500.12105/150452025-06-26T10:47:39Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616col_20.500.12105_25179

00925njm 22002777a 4500 dc Baladron-Jimenez, Beatriz Isabel author Mirela Mielu, Lidia author Lopez-Martin, Estrella author Barrero, Maria author López-Jiménez, Lidia author Alvarado, Jose I author Monzon-Fernandez, Sara author Varona Fernandez, Sarai author Cuesta de la Plaza, Isabel author Cazorla, Rosario author Lara, Julián author Iglesias, Gemma author Román, Enriqueta author Ros, Purificación author Gomez-Mariano, Gema Maria author Cubillo, Isabel author Hernandez-SanMiguel, Esther author Rivera Pinto, Daniel author Alonso, Javier author Bermejo-Sanchez, Eva author Posada De la Paz, Manuel author Martinez-Delgado, Beatriz author 2022-08-22 Pathogenic hemizygous or heterozygous mutations in the IQSEC2 gene cause X-linked intellectual developmental disorder-1 (XLID1), characterized by a variable phenotype including developmental delay, intellectual disability, epilepsy, hypotonia, autism, microcephaly and stereotypies. It affects both males and females typically through loss of function in males and haploinsufficiency in heterozygous females. Females are generally less affected than males. Two novel unrelated cases, one male and one female, with de novo IQSEC2 variants were detected by trio-based whole exome sequencing. The female case had a previously undescribed frameshift mutation (NM_001111125:c.3300dup; p.Met1101Tyrfs*5), and the male showed an intronic variant in intron 6, with a previously unknown effect (NM_001111125:c.2459+21C>T). IQSEC2 gene expression study revealed that this intronic variant created an alternative donor splicing site and an aberrant product, with the inclusion of 19bp, confirming the pathogenic effect of the intron variant. Moreover, a strong reduction in the expression of the long, but also the short IQSEC2 isoforms, was detected in the male correlating with a more severe phenotype, while the female case showed no decreased expression of the short isoform, and milder effects of the disease. This suggests that the abnormal expression levels of the different IQSEC2 transcripts could be implicated in the severity of disease manifestations. Int J Mol Sci. 2022 Aug 22;23(16):9480. 10.3390/ijms23169480 1422-0067 International journal of molecular sciences 36012761 http://hdl.handle.net/20.500.12105/15045 IQSEC2 gene Neurodevelopment syndrome Exome Transcript isoforms Intron variant Gene expression Spain UDP Differences in Expression of IQSEC2 Transcript Isoforms in Male and Female Cases with Loss of Function Variants and Neurodevelopmental Disorder