Media type: E-Article Title: Microdeletion of Xq28 involving the AFF2 (FMR2) gene in two unrelated males with developmental delay Contributor: Sahoo, Trilochan; Theisen, Aaron; Marble, Michael; Tervo, Raymond; Rosenfeld, Jill A.; Torchia, Beth S.; Shaffer, Lisa G. imprint: Wiley, 2011 Published in: American Journal of Medical Genetics Part A Language: English DOI: 10.1002/ajmg.a.34345 ISSN: 1552-4825; 1552-4833 Keywords: Genetics (clinical) ; Genetics Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>Fragile X E (FRAXE) is an X‐linked form of intellectual disability characterized by mild to moderate cognitive impairment, speech delay, hyperactivity, and autistic behavior. The folate‐sensitive fragile site FRAXE is located in Xq28 approximately 600 kb distal to the fragile X syndrome fragile site (FRAXA) and harbors an unstable GCC (CCG) triplet repeat adjacent to a CpG island in the 5′ untranslated region of the <jats:italic>AFF2</jats:italic> (<jats:italic>FMR2</jats:italic>) gene. The disorder results from amplification and methylation of the GCC repeat and resultant silencing of <jats:italic>AFF2</jats:italic>. Although chromosome abnormalities that disrupt <jats:italic>AFF2</jats:italic> have been reported in two individuals with mild‐moderate intellectual disability, microdeletions of Xq28 that delete only <jats:italic>AFF2</jats:italic> have not been described as a potential cause of FRAXE‐intellectual disability. We performed clinical and molecular characterization of two males with 240 and 499 kb deletions, respectively, at Xq28, both of which encompassed only one gene, <jats:italic>AFF2</jats:italic>. The 240 kb deletion in Patient 1 was intragenic and lead to the loss of 5′ exons 2–4 of <jats:italic>AFF2</jats:italic>; the 499 kb deletion in Patient 2 removed the 5′ exons 1–2 of <jats:italic>AFF2</jats:italic> including approximately 350 kb upstream of the gene. Both individuals had developmental and speech delay, and one had mild dysmorphism. We predict disruption of <jats:italic>AFF2</jats:italic> in these two patients is likely the cause of their overlapping phenotypes. © 2011 Wiley Periodicals, Inc.</jats:p>