Novel no‐stop FLNA mutation causes multi‐organ involvement in males. Issue 9 (19th July 2013)

• Record Type: Journal Article
• Authors: Oegema, Renske; Hulst, Jessie M.; Theuns‐Valks, Sabine D.M.; van Unen, Leontine M.A.; Schot, Rachel; Mancini, Grazia M.S.; Schipper, Marguerite E.I.; de Wit, Marie C.Y.; Sibbles, Barbara J.; de Coo, Irenaeus F.M.; Nanninga, Veerle; Hofstra, Robert M.W.; Halley, Dicky J.J.; Brooks, Alice S.
• Is Part Of: American journal of medical genetics. Volume 161:Issue 9(2013:Sep.)
• Page Start: 2376
• Page End: 2384
• Publication Date: 2013-07-19
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36109
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="ajmga36109-sec-0001" sec-type="section"> <p>Mutations in <italic>FLNA</italic> (Filamin A, OMIM 300017) cause X‐linked periventricular nodular heterotopia (XL‐PNH). XL‐PNH‐associated mutations are considered lethal in hemizygous males. However, a few males with unusual mutations (including distal truncating and hypomorphic missense mutations), and somatic mosaicism have been reported to survive past infancy. Two brothers had an atypical presentation with failure to thrive and distinct facial appearance including hypertelorism. Evaluations of these brothers and their affected cousin showed systemic involvement including severe intestinal malfunction, malrotation, congenital short bowel, PNH, pyloric stenosis, wandering spleen, patent ductus arteriosus, atrial septal defect, inguinal hernia, and vesicoureteral reflux. The unanticipated finding of PNH led to <italic>FLNA</italic> testing and subsequent identification of a novel no‐stop <italic>FLNA</italic> mutation (c.7941_7942delCT, p.(*2648Serext*100)). Western blotting and qRT‐PCR of patients' fibroblasts showed diminished levels of protein and mRNA. This <italic>FLNA</italic> mutation, the most distal reported so far, causes in females classical XL‐PNH, but in males an unusual, multi‐organ phenotype, providing a unique insight into the <italic>FLNA</italic>‐associated phenotypes. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>