Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability. Issue 10 (26th July 2020)

• Record Type: Journal Article
• Authors: Mehvari, Sepideh; Larti, Farzaneh; Hu, Hao; Fattahi, Zohreh; Beheshtian, Maryam; Abedini, Seyedeh Sedigheh; Arzhangi, Sanaz; Ropers, Hans‐Hilger; Kalscheuer, Vera M.; Auld, Daniel; Kahrizi, Kimia; Riazalhosseini, Yasser; Najmabadi, Hossein
• Is Part Of: Molecular genetics & genomic medicine. Volume 8:Issue 10(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-07-26
• Subjects: intellectual disability -- whole genome sequencing -- Xq duplication -- Xq13.2q13.3; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1418
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: The X chromosome has historically been one of the most thoroughly investigated chromosomes regarding intellectual disability (ID), whose etiology is attributed to many factors including copy number variations (CNVs). Duplications of the long arm of the X chromosome have been reported in patients with ID, short stature, facial anomalies, and in many cases hypoplastic genitalia and/or behavioral abnormalities. Methods: Here, we report on a large Iranian family with X‐linked ID caused by a duplication on the X chromosome identified by whole genome sequencing in combination with linkage analysis. Results: Seven affected males in different branches of the family presented with ID, short stature, seizures, facial anomalies, behavioral abnormalities (aggressiveness, self‐injury, anxiety, impaired social interactions, and shyness), speech impairment, and micropenis. The duplication of the region Xq13.2q13.3, which is ~1.8 Mb in size, includes seven protein‐coding OMIM genes. Three of these genes, namely SLC16A2, RLIM, and NEXMIF, if impaired, can lead to syndromes presenting with ID. Of note, this duplicated region was located within a linkage interval with a LOD score >3. Conclusion: Our report indicates that CNVs should be considered in multi‐affected families where no candidate gene defect has been identified in sequencing data analysis. Abstract : We report a duplication on the X chromosome encompassing Xq13.2q13.3 in a large Iranian family with X‐linked intellectual disability. There are seven affected males in ones and twos within two generations of the pedigree who presented with a similar phenotype, including ID, short stature, seizures, facial anomalies, behavioral abnormalities, speech impairment, and micropenis.