1. IQSEC2 disorder: A new disease entity or a Rett spectrum continuum?
- Author
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Anna Maria Pinto, Giuseppe Castello, Lionel Van Maldergem, Caterina Lo Rizzo, Alessandra Ferrarini, Vittoria Lamacchia, Jeroen Breckpot, Candy Kumps, Damien Lederer, Francesca Mari, Alessandra Renieri, Mercè Pineda, Elisabetta Vaghi, Diego Lopergolo, Judith Armstrong, Francesca Ariani, Maria Del Carmen Fons-Estupina, Flavia Privitera, Mercedes Serrano, Sabrina Mueller, Gian Paolo Ramelli, Roberto Canitano, Bert Callewaert, Gerardo Mejia Baltodano, Hilde Van Esch, Maria Antonietta Mencarelli, and Aurora Currò
- Subjects
0301 basic medicine ,Male ,INTELLECTUAL DISABILITY ,030105 genetics & heredity ,Bioinformatics ,phenotype-genotype ,IQSEC2 ,Rett syndrome ,Intellectual disability ,Medicine and Health Sciences ,Guanine Nucleotide Exchange Factors ,Genetics(clinical) ,intellectual disability ,Child ,Genetics (clinical) ,Clinical course ,Middle Aged ,Phenotype ,New disease ,Child, Preschool ,Phenotype genotype ,INACTIVATION ,Female ,Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,PHENOTYPIC VARIABILITY ,Diagnosis, Differential ,03 medical and health sciences ,Young Adult ,Intellectual Disability ,Exome Sequencing ,Genetics ,medicine ,Rett Syndrome ,Humans ,Point Mutation ,Genetic Association Studies ,LANDSCAPE ,MUTATIONS ,business.industry ,Point mutation ,medicine.disease ,GENE ,030104 developmental biology ,Differential diagnosis ,business - Abstract
IQSEC2 mutations are associated with IQSEC2-related intellectual disability (ID). Phenotypic spectrum has been better defined in the last few years by the increasing number of reported cases although the genotype-phenotype relationship for IQSEC2 remains overall complex. As for IQSEC2-related ID a wide phenotypic diversity has been described in Rett syndrome (RTT). Several patients harboring IQSEC2 mutations present with clinical symptoms similar to RTT and some cases meet most of the criteria for classic RTT. With the aim of establishing a genotype-phenotype correlation, we collected data of 16 patients harboring IQSEC2 point mutations (15 of them previously unreported) and of five novel patients carrying CNVs encompassing IQSEC2. Most of our patients surprisingly shared a moderate-to-mild phenotype. The similarities in the clinical course between our mild cases and patients with milder forms of atypical RTT reinforce the hypothesis that also IQSEC2 mutated patients may lay under the wide clinical spectrum of RTT and thus IQSEC2 should be considered in the differential diagnosis. Our data confirm that position, type of variant and gender are crucial for IQSEC2-associated phenotype delineation.
- Published
- 2020