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Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: Relationship to SFTPB
Author(s) -
Tredano Mohammed,
Griese Matthias,
de Blic Jacques,
Lorant Tifenn,
Houdayer Claude,
Schumacher Silja,
Cartault François,
Capron Frédérique,
BocconGibod Liliane,
LacazeMasmonteil Thierry,
Renolleau Sylvain,
Delaisi Bertrand,
Elion Jacques,
Couderc Rémy,
Bahuau Michel
Publication year - 2003
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.20058
Subject(s) - penetrance , proband , consanguinity , population , medicine , genetics , respiratory distress , genetic heterogeneity , genetic counseling , founder effect , pediatrics , biology , mutation , genotype , gene , haplotype , surgery , phenotype , environmental health
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. © 2003 Wiley‐Liss, Inc.