title: Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: relationship to SFTPB.
abstract: We have analyzed surfactant protein B (SP-B) and its encoding gene (SFTPB, MIM 178640) in 40 unrelated pediatric patients with unexplained respiratory distress (URD). There was high consanguinity (eight kindreds) and an underlying autosomal recessive trait could be inferred in most cases, with overall high sex ratio (32/17) suggesting proband's gender to impact on penetrance. The clinical/biological presentations fitted into three major nosologic frameworks. I: SP-B deficiency (nine probands), complete or incomplete, with homozygous/compoundly heterozygous mutations identified (six probands), including one from the population isolate of Réunion Island (496delG). In addition, there was a consanguineous kindred in which incomplete deficiency was unambiguously unlinked to SFTPB. II: pulmonary alveolar proteinosis (PAP, 19 probands), with typical storage of PAS-positive material within the alveoli with foamy macrophages and variable interstitial reaction, which was diagnosed in most patients from Réunion Island. In contrast to previously published findings, mutation and/or segregation analyses excluded SFTPB as a disease locus, although slight metabolic derangement related to SP-B and/or mild SFTPB changes could somehow contribute to disease. III: URD without evidence for SP-B deficiency or PAP (12 probands), equally unlinked to SFTPB, although a single patient had a possibly causal, maternally-derived, heterozygous genetic change (G4521A). The population frequency of five known and four novel SNPs was studied, providing as many potential markers for pulmonary disease related to SFTPB. Overall, URD was found to be heterogeneous, both phenotypically and genetically, even in population isolates where a founder effect might have been expected. When disease loci are identified, patient genotyping will be crucial as a diagnostic aid, for devising proper treatment, and as a basis for genetic counseling.
authors.affiliation: Service de Biochimie et Biologie Moléculaire, Hôpital d'Enfants Armand-Trousseau (AP-HP), Paris, France. assistants.bm@trs.ap-hop-paris.fr
authors.forename: Mohammed
authors.initials: M
authors.lastname: Tredano
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Jacques
authors.initials: J
authors.lastname: de Blic
authors.forename: Tifenn
authors.initials: T
authors.lastname: Lorant
authors.forename: Claude
authors.initials: C
authors.lastname: Houdayer
authors.forename: Silja
authors.initials: S
authors.lastname: Schumacher
authors.forename: François
authors.initials: F
authors.lastname: Cartault
authors.forename: Frédérique
authors.initials: F
authors.lastname: Capron
authors.forename: Liliane
authors.initials: L
authors.lastname: Boccon-Gibod
authors.forename: Thierry
authors.initials: T
authors.lastname: Lacaze-Masmonteil
authors.forename: Sylvain
authors.initials: S
authors.lastname: Renolleau
authors.forename: Bertrand
authors.initials: B
authors.lastname: Delaisi
authors.forename: Jacques
authors.initials: J
authors.lastname: Elion
authors.forename: Rémy
authors.initials: R
authors.lastname: Couderc
authors.forename: Michel
authors.initials: M
authors.lastname: Bahuau
mesh_terms: D000595:Amino Acid Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000097:blood; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D011649:Pulmonary Alveolar Proteinosis / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics*; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000378:metabolism; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D037701:Pulmonary Surfactant-Associated Protein B; D011663:Pulmonary Surfactants; D004247:DNA