title: Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.
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.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. psen@bcm.edu
authors.forename: Partha
authors.initials: P
authors.lastname: Sen
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.forename: Colby
authors.initials: C
authors.lastname: Navarro
authors.forename: Iris
authors.initials: I
authors.lastname: Silva
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Szafranski
authors.forename: Katarzyna E
authors.initials: KE
authors.lastname: Kolodziejska
authors.forename: Avinash V
authors.initials: AV
authors.lastname: Dharmadhikari
authors.forename: Hasnaa
authors.initials: H
authors.lastname: Mostafa
authors.forename: Harry
authors.initials: H
authors.lastname: Kozakewich
authors.forename: Debra
authors.initials: D
authors.lastname: Kearney
authors.forename: John B
authors.initials: JB
authors.lastname: Cahill
authors.forename: Merrissa
authors.initials: M
authors.lastname: Whitt
authors.forename: Masha
authors.initials: M
authors.lastname: Bilic
authors.forename: Linda
authors.initials: L
authors.lastname: Margraf
authors.forename: Adrian
authors.initials: A
authors.lastname: Charles
authors.forename: Jack
authors.initials: J
authors.lastname: Goldblatt
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gibson
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Lantz
authors.forename: A Julian
authors.initials: AJ
authors.lastname: Garvin
authors.forename: John
authors.initials: J
authors.lastname: Petty
authors.forename: Zeina
authors.initials: Z
authors.lastname: Kiblawi
authors.forename: Craig
authors.initials: C
authors.lastname: Zuppan
authors.forename: Allyn
authors.initials: A
authors.lastname: McConkie-Rosell
authors.forename: Marie T
authors.initials: MT
authors.lastname: McDonald
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Peterson-Carmichael
authors.forename: Jane T
authors.initials: JT
authors.lastname: Gaede
authors.forename: Binoy
authors.initials: B
authors.lastname: Shivanna
authors.forename: Deborah
authors.initials: D
authors.lastname: Schady
authors.forename: Philippe S
authors.initials: PS
authors.lastname: Friedlich
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Hays
authors.forename: Irene Valenzuela
authors.initials: IV
authors.lastname: Palafoll
authors.forename: Ulrike
authors.initials: U
authors.lastname: Siebers-Renelt
authors.forename: Axel
authors.initials: A
authors.lastname: Bohring
authors.forename: Laura S
authors.initials: LS
authors.lastname: Finn
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Siebert
authors.forename: Csaba
authors.initials: C
authors.lastname: Galambos
authors.forename: Lananh
authors.initials: L
authors.lastname: Nguyen
authors.forename: Melissa
authors.initials: M
authors.lastname: Riley
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.forename: Adeline
authors.initials: A
authors.lastname: Vigouroux
authors.forename: Gustavo
authors.initials: G
authors.lastname: Rocha
authors.forename: Susana
authors.initials: S
authors.lastname: Fernandes
authors.forename: Jane
authors.initials: J
authors.lastname: Brumbaugh
authors.forename: Kari
authors.initials: K
authors.lastname: Roberts
authors.forename: Luk
authors.initials: L
authors.lastname: Ho-Ming
authors.forename: Ivan F M
authors.initials: IF
authors.lastname: Lo
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
authors.forename: Romana
authors.initials: R
authors.lastname: Gerychova
authors.forename: Marta
authors.initials: M
authors.lastname: Jezova
authors.forename: Iveta
authors.initials: I
authors.lastname: Valaskova
authors.forename: Florence
authors.initials: F
authors.lastname: Fellmann
authors.forename: Katayoun
authors.initials: K
authors.lastname: Afshar
authors.forename: Eric
authors.initials: E
authors.lastname: Giannoni
authors.forename: Vincent
authors.initials: V
authors.lastname: Muhlethaler
authors.forename: Jinlong
authors.initials: J
authors.lastname: Liang
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Janet
authors.initials: J
authors.lastname: Lioy
authors.forename: Hitesh
authors.initials: H
authors.lastname: Deshmukh
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Srinivasan
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Swarr
authors.forename: Melissa
authors.initials: M
authors.lastname: Sloman
authors.forename: Charles
authors.initials: C
authors.lastname: Shaw-Smith
authors.forename: Rosa Laura
authors.initials: RL
authors.lastname: van Loon
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hagman
authors.forename: Yves
authors.initials: Y
authors.lastname: Sznajer
authors.forename: Catherine
authors.initials: C
authors.lastname: Barrea
authors.forename: Christine
authors.initials: C
authors.lastname: Galant
authors.forename: Thierry
authors.initials: T
authors.lastname: Detaille
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wambach
authors.forename: F Sessions
authors.initials: FS
authors.lastname: Cole
authors.forename: Aaron
authors.initials: A
authors.lastname: Hamvas
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Prince
authors.forename: Karin E M
authors.initials: KE
authors.lastname: Diderich
authors.forename: Alice S
authors.initials: AS
authors.lastname: Brooks
authors.forename: Robert M
authors.initials: RM
authors.lastname: Verdijk
authors.forename: Hari
authors.initials: H
authors.lastname: Ravindranathan
authors.forename: Ella
authors.initials: E
authors.lastname: Sugo
authors.forename: David
authors.initials: D
authors.lastname: Mowat
authors.forename: Michael L
authors.initials: ML
authors.lastname: Baker
authors.forename: Claire
authors.initials: C
authors.lastname: Langston
authors.forename: Stephen
authors.initials: S
authors.lastname: Welty
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
mesh_terms: D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D030541:Databases, Genetic; D005260:Female; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018628:Gene Dosage; D023061:Gene Order; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010547:Persistent Fetal Circulation Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors