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Novel no‐stop FLNA mutation causes multi‐organ involvement in males
Author(s) -
Oegema Renske,
Hulst Jessie M.,
TheunsValks 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.
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36109
Subject(s) - flna , filamin , missense mutation , failure to thrive , intestinal malrotation , hypertelorism , medicine , phenotype , genetics , germline mutation , mutation , biology , gene , cytoskeleton , cell
Mutations in FLNA (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 FLNA testing and subsequent identification of a novel no‐stop FLNA mutation (c.7941_7942delCT, p.(*2648Serext*100)). Western blotting and qRT‐PCR of patients' fibroblasts showed diminished levels of protein and mRNA. This FLNA 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 FLNA ‐associated phenotypes. © 2013 Wiley Periodicals, Inc.