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Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain
Author(s) -
Sen Partha,
Yang Yaping,
Navarro Colby,
Silva Iris,
Szafranski Przemyslaw,
Kolodziejska Katarzyna E.,
Dharmadhikari Avinash V.,
Mostafa Hasnaa,
Kozakewich Harry,
Kearney Debra,
Cahill John B.,
Whitt Merrissa,
Bilic Masha,
Margraf Linda,
Charles Adrian,
Goldblatt Jack,
Gibson Kathleen,
Lantz Patrick E.,
Garvin A. Julian,
Petty John,
Kiblawi Zeina,
Zuppan Craig,
McConkieRosell Allyn,
McDonald Marie T.,
PetersonCarmichael Stacey L.,
Gaede Jane T.,
Shivanna Binoy,
Schady Deborah,
Friedlich Philippe S.,
Hays Stephen R.,
Palafoll Irene Valenzuela,
SiebersRenelt Ulrike,
Bohring Axel,
Finn Laura S.,
Siebert Joseph R.,
Galambos Csaba,
Nguyen Lananh,
Riley Melissa,
Chassaing Nicolas,
Vigouroux Adeline,
Rocha Gustavo,
Fernandes Susana,
Brumbaugh Jane,
Roberts Kari,
Homing Luk,
Lo Ivan F. M.,
Lam Stephen,
Gerychova Romana,
Jezova Marta,
Valaskova Iveta,
Fellmann Florence,
Afshar Katayoun,
Giani Eric,
Muhlethaler Vincent,
Liang Jinlong,
Beckmann Jacques S.,
Lioy Janet,
Deshmukh Hitesh,
Srinivasan Lakshmi,
Swarr Daniel T.,
Sloman Melissa,
ShawSmith Charles,
Loon Rosa Laura,
Hagman Cecilia,
Sznajer Yves,
Barrea Catherine,
Galant Christine,
Detaille Thierry,
Wambach Jennifer A.,
Cole F. Sessions,
Hamvas Aaron,
Prince Lawrence S.,
Diderich Karin E.M.,
Brooks Alice S.,
Verdijk Robert M.,
Ravindranathan Hari,
Sugo Ella,
Mowat David,
Baker Michael L.,
Langston Claire,
Welty Stephen,
Stankiewicz Pawel
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22313
Subject(s) - biology , genetics , missense mutation , point mutation , frameshift mutation , nonsense mutation , renal dysplasia , exon , haploinsufficiency , nonsynonymous substitution , mutation , dysplasia , gene , genome , kidney , phenotype
ABSTRACT Alveolar capillary dysplasia with misalignment of pulmonary veins ( ACD / MPV ) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD / MPV . We have collected DNA and pathological samples from more than 90 infants with ACD / MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA ‐binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1 . These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD / MPV and lung organogenesis.