X‐linked CHARGE‐like Abruzzo–Erickson syndrome and classic cleft palate with ankyloglossia result from TBX22 splicing mutations. (7th August 2012)

• Record Type: Journal Article
• Authors: Pauws, E; Peskett, E; Boissin, C; Hoshino, A; Mengrelis, K; Carta, E; Abruzzo, MA; Lees, M; Moore, GE; Erickson, RP; Stanier, P
• Is Part Of: Clinical genetics. Volume 83:Number 4(2013:Apr.)
• Page Start: 352
• Page End: 358
• Publication Date: 2012-08-07
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/j.1399-0004.2012.01930.x
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>X‐linked cleft palate (CPX) is caused by mutations in the gene encoding the TBX22 transcription factor and is known to exhibit phenotypic variability, usually involving either a complete, partial or submucous cleft palate, with or without ankyloglossia. This study hypothesized a possible involvement of TBX22 in a family with X‐linked, CHARGE‐like Abruzzo–Erickson syndrome, of unknown etiology. The phenotype extends to additional features including sensorineural deafness and coloboma, which are suggested by the <italic>Tbx22</italic> developmental expression pattern but not previously associated in CPX patients. A novel <italic>TBX22</italic> splice acceptor mutation (c.593−5T>A) was identified that tracked with the phenotype in this family. A novel splice donor variant (c.767+5G>A) and a known canonical splice donor mutation (c.767+1G>A) affecting the same exon were identified in patients with classic CPX phenotypes and were comparatively analyzed using both <italic>in silico</italic> and <italic>in vitro</italic> splicing studies. All three variants were predicted to abolish normal mRNA splicing and an <italic>in vitro</italic> assay indicated that use of alternative splice sites was a likely outcome. Collectively, the data showed the functional effect of several novel intronic splice site variants but most importantly confirms that <italic>TBX22</italic> is the gene underlying Abruzzo–Erickson syndrome, expanding the phenotypic spectrum of <italic>TBX22</italic> mutations.</p> </abstract>