Identification of microduplications at Xp21.2 and Xq13.1 in neurodevelopmental disorders

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Kokkonen , H , Siren , A , Määttä , T , Kamila Kadlubowska , M , Acharya , A , Nouel-Saied , L M , Leal , S M , Jarvela , I & Schrauwen , I 2021 , ' Identification of microduplications at Xp21.2 and Xq13.1 in neurodevelopmental disorders ' , Molecular Genetics & Genomic Medicine , vol. 9 , no. 12 , 1703 .

Title: Identification of microduplications at Xp21.2 and Xq13.1 in neurodevelopmental disorders
Author: Kokkonen, Hannaleena; Siren, Auli; Määttä, Tuomo; Kamila Kadlubowska, Magda; Acharya, Anushree; Nouel-Saied, Liz M.; Leal, Suzanne M.; Jarvela, Irma; Schrauwen, Isabelle
Contributor organization: Irma Järvelä / Principal Investigator
Department of Medical and Clinical Genetics
University of Helsinki
Date: 2021-12
Language: eng
Number of pages: 8
Belongs to series: Molecular Genetics & Genomic Medicine
ISSN: 2324-9269
Abstract: Background: Microduplications are a rare cause of disease in X-linked neurodevelopmental disorders but likely have been under reported due challenges in detection and interpretation. Methods: We performed exome sequencing and subsequent microarray analysis in two families with a neurodevelopmental disorder. Results: Here, we report on two families each with unique inherited microduplications at Xp21.2 and Xq13.1, respectively. In the first family, a 562.8-kb duplication at Xq13.1 covering DLG3, TEX11, SLC7A3, GDPD2, and part KIF4A was identified in a boy whose phenotype was characterized by delayed speech development, mild intellectual disability (ID), mild dysmorphic facial features, a heart defect, and neuropsychiatric symptoms. By interrogating all reported Xq13.1 duplications in individuals affected with a neurodevelopmental disorder, we provide evidence that this genomic region and particularly DLG3 might be sensitive to an increased dosage. In the second family with four affected males, we found a noncontinuous 223- and 204-kb duplication at Xp21.2, of which the first duplication covers exon 6 of IL1RAPL1. The phenotype of the male patients was characterized by delayed speech development, mild to moderate ID, strabismus, and neurobehavioral symptoms. The carrier daughter and her mother had learning difficulties. IL1RAPL1 shows nonrecurrent causal structural variation and is located at a common fragile site (FRAXC), prone to re-arrangement. Conclusion: In conclusion, we show that comprehensive clinical and genetic examination of microduplications on the X-chromosome can be helpful in undiagnosed cases of neurodevelopmental disease.
Subject: exome sequencing
intellectual disability
neurodevelopmental disorders
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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