Duplication at Xq13.3–q21.1 with syndromic intellectual disability, a probable role for the ATRX gene. Issue 4 (23rd January 2014)

• Record Type: Journal Article
• Authors: Martínez, Francisco; Roselló, Mónica; Mayo, Sonia; Monfort, Sandra; Oltra, Silvestre; Orellana, Carmen
• Is Part Of: American journal of medical genetics. Volume 164:Issue 4(2014.)
• Page Start: 918
• Page End: 923
• Publication Date: 2014-01-23
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36371
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36371-sec-0001" sec-type="section"> <p>Here we report on two unrelated male patients with syndromic intellectual disability (ID) due to duplication at Xq13.3–q21.1, a region of about 6 Mb and 25 genes. Among these, the most outstanding is <italic>ATRX</italic>, the causative gene of X‐linked alpha‐thalassemia/mental retardation. <italic>ATRX</italic> belongs to the growing list of genes implied in chromatin remodeling causing ID. Many these genes, such as <italic>MECP2</italic>, are dose‐sensitive so that not only deletions and point mutations, but also duplications cause ID. Both patients have severe ID, absent expressive speech, early hypotonia, behavior problems (hyperactivity, repetitive self‐stimulatory behavior), postnatal growth deficiency, microcephaly, micrognathia, cryptorchidism, low‐set, posteriorly angulated ears, and downslanting palpebral fissures. These findings are also usually present among patients with loss‐of‐function mutations of the <italic>ATRX</italic> gene. Completely skewed X inactivation was observed in the only informative carrier mother, a constant finding among female carriers of inactivating point mutations of this gene. Participation of other duplicated genes cannot be excluded; nevertheless we propose that the increased dosage of <italic>ATRX</italic> is the major pathogenic mechanism of this X‐linked disorder, a syndrome reminiscent of <italic>MECP2</italic> duplication. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>