title: Null ABCA3 in humans: large homozygous ABCA3 deletion, correlation to clinical-pathological findings.
abstract: A study was undertaken to analyze the clinical presentation, pulmonary function, and pathological features in two female siblings with neonatal pulmonary surfactant metabolism dysfunction, type 3 (MIM 610921). The clinical records of the siblings were examined; the genes encoding surfactant protein B (SFTPB), surfactant protein C (SFTPC), and ATP-binding cassette transporter 3 protein (ABCA3) were analyzed with direct sequencing and Southern blotting. The infants were homozygous for a 5,983 bp deletion in ABCA3 including exons 2-5 as well as the start AUG codon and a putative Golgi exit signal motif. Dense abnormalities of lamellar bodies at electron microscopy and absence of ABCA3 at immunohistochemical staining were in agreement with the presence of two null alleles. In addition, an increased lipid synthesis suggested a compensatory mechanism. The clinical course in the two sisters was influenced by different environmental factors like the time needed for molecular confirmation, the ventilatory assistance adopted, the occurrence of infections. A less aggressive clinical approach did not improve the course of the disease; the prognosis was always poor. Development of a fast molecular test, able to detect also structural variants, is needed.
authors.affiliation: Unit of Genomics for Human Disease Diagnosis, Centre of Translational Genomics and Bioinformatics, Ospedale San Raffaele, Milano, Italy; Laboraf, Diagnostica e Ricerca, Ospedale San Raffaele, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Carrera
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ferrari
authors.forename: Silvia
authors.initials: S
authors.lastname: Presi
authors.forename: Luisa
authors.initials: L
authors.lastname: Ventura
authors.forename: Barbara
authors.initials: B
authors.lastname: Vergani
authors.forename: Valeria
authors.initials: V
authors.lastname: Lucchini
authors.forename: Paola E
authors.initials: PE
authors.lastname: Cogo
authors.forename: Virgilio P
authors.initials: VP
authors.lastname: Carnielli
authors.forename: Marco
authors.initials: M
authors.lastname: Somaschini
authors.forename: Paolo
authors.initials: P
authors.lastname: Tagliabue
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000172:deficiency / Q000235:genetics*; D015139:Blotting, Southern; D017809:Fatal Outcome; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D017563:Lung Diseases, Interstitial / Q000175:diagnosis / Q000235:genetics; D012127:Respiratory Distress Syndrome, Newborn / Q000175:diagnosis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D035781:Siblings
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters
keywords: ABCA3; molecular diagnostic testing; newborn; patient care management; respiratory distress syndrome; sequence deletion