Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency

D. E. DeMello, Lawrence Nogee, S. Heyman, H. F. Krous, M. Hussain, T. A. Merritt, W. Hsueh, J. E. Haas, K. Heidelberger, R. Schumacher, H. R. Colten

Research output: Contribution to journalArticle

Abstract

Congenital alveolar proteinosis (CAP) is an often fatal cause af respiratory failure in term newborn infants, which has been associated with a genetic deficiency of surfactant protein B (SP-B) as a result of a frameshift mutation (121ins2) in a family with three affected siblings. In the index cases the deficiency of SP-B was associated with qualitative and quantitative abnormalities of the surfactant proteins A and C. Immunostaining for lung surfactant proteins and a search for the 121ins2 mutation by restriction enzyme analysis of DNA extracted from paraffin-embedded lung tissue was performed for 7 additional affected infants from 6 families, bringing to 10 the total number of patients with CAP who have been studied. In six infants, the surfactant protein immunostaining pattern was similar to that of the index cases. Of these, three patients were homozygous for the 121ins2 mutation; one was a compound heterozygote with the 121ins2 in one allele and a different mutation in the other; and three patients lacked the mutation in both alleles. One infant had an abundance of SP-B, suggesting phenotypic heterogeneity in CAP. Lung ultrastructural abnormalities, such as a reduced number of lamellar bodies, absent tubular myelin, and basal secretion of surfactant lipids and proteins, suggest a significant derangement of surfactant metabolism. The phenotypic heterogeneity in infants with CAP raises the possibility that variable degrees of SP-B deficiency may be more common than previously suspected.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalJournal of Pediatrics
Volume125
Issue number1
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Surface-Active Agents
Mutation
Pulmonary Surfactant-Associated Proteins
Alleles
Pulmonary Surfactant-Associated Protein A
Lung
Restriction Mapping
Frameshift Mutation
Heterozygote
Protein C
Respiratory Insufficiency
Paraffin
Siblings
Proteins
Newborn Infant
Lipids
Congenital Deficiency of Pulmonary Surfactant Protein B
DNA

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency. / DeMello, D. E.; Nogee, Lawrence; Heyman, S.; Krous, H. F.; Hussain, M.; Merritt, T. A.; Hsueh, W.; Haas, J. E.; Heidelberger, K.; Schumacher, R.; Colten, H. R.

In: Journal of Pediatrics, Vol. 125, No. 1, 1994, p. 43-50.

Research output: Contribution to journalArticle

DeMello, DE, Nogee, L, Heyman, S, Krous, HF, Hussain, M, Merritt, TA, Hsueh, W, Haas, JE, Heidelberger, K, Schumacher, R & Colten, HR 1994, 'Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency', Journal of Pediatrics, vol. 125, no. 1, pp. 43-50. https://doi.org/10.1016/S0022-3476(94)70119-9
DeMello, D. E. ; Nogee, Lawrence ; Heyman, S. ; Krous, H. F. ; Hussain, M. ; Merritt, T. A. ; Hsueh, W. ; Haas, J. E. ; Heidelberger, K. ; Schumacher, R. ; Colten, H. R. / Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency. In: Journal of Pediatrics. 1994 ; Vol. 125, No. 1. pp. 43-50.
@article{fcbed3beb2954661bc4dc5ce0bde5708,
title = "Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency",
abstract = "Congenital alveolar proteinosis (CAP) is an often fatal cause af respiratory failure in term newborn infants, which has been associated with a genetic deficiency of surfactant protein B (SP-B) as a result of a frameshift mutation (121ins2) in a family with three affected siblings. In the index cases the deficiency of SP-B was associated with qualitative and quantitative abnormalities of the surfactant proteins A and C. Immunostaining for lung surfactant proteins and a search for the 121ins2 mutation by restriction enzyme analysis of DNA extracted from paraffin-embedded lung tissue was performed for 7 additional affected infants from 6 families, bringing to 10 the total number of patients with CAP who have been studied. In six infants, the surfactant protein immunostaining pattern was similar to that of the index cases. Of these, three patients were homozygous for the 121ins2 mutation; one was a compound heterozygote with the 121ins2 in one allele and a different mutation in the other; and three patients lacked the mutation in both alleles. One infant had an abundance of SP-B, suggesting phenotypic heterogeneity in CAP. Lung ultrastructural abnormalities, such as a reduced number of lamellar bodies, absent tubular myelin, and basal secretion of surfactant lipids and proteins, suggest a significant derangement of surfactant metabolism. The phenotypic heterogeneity in infants with CAP raises the possibility that variable degrees of SP-B deficiency may be more common than previously suspected.",
author = "DeMello, {D. E.} and Lawrence Nogee and S. Heyman and Krous, {H. F.} and M. Hussain and Merritt, {T. A.} and W. Hsueh and Haas, {J. E.} and K. Heidelberger and R. Schumacher and Colten, {H. R.}",
year = "1994",
doi = "10.1016/S0022-3476(94)70119-9",
language = "English (US)",
volume = "125",
pages = "43--50",
journal = "Journal of Pediatrics",
issn = "0022-3476",
publisher = "Mosby Inc.",
number = "1",

}

TY - JOUR

T1 - Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency

AU - DeMello, D. E.

AU - Nogee, Lawrence

AU - Heyman, S.

AU - Krous, H. F.

AU - Hussain, M.

AU - Merritt, T. A.

AU - Hsueh, W.

AU - Haas, J. E.

AU - Heidelberger, K.

AU - Schumacher, R.

AU - Colten, H. R.

PY - 1994

Y1 - 1994

N2 - Congenital alveolar proteinosis (CAP) is an often fatal cause af respiratory failure in term newborn infants, which has been associated with a genetic deficiency of surfactant protein B (SP-B) as a result of a frameshift mutation (121ins2) in a family with three affected siblings. In the index cases the deficiency of SP-B was associated with qualitative and quantitative abnormalities of the surfactant proteins A and C. Immunostaining for lung surfactant proteins and a search for the 121ins2 mutation by restriction enzyme analysis of DNA extracted from paraffin-embedded lung tissue was performed for 7 additional affected infants from 6 families, bringing to 10 the total number of patients with CAP who have been studied. In six infants, the surfactant protein immunostaining pattern was similar to that of the index cases. Of these, three patients were homozygous for the 121ins2 mutation; one was a compound heterozygote with the 121ins2 in one allele and a different mutation in the other; and three patients lacked the mutation in both alleles. One infant had an abundance of SP-B, suggesting phenotypic heterogeneity in CAP. Lung ultrastructural abnormalities, such as a reduced number of lamellar bodies, absent tubular myelin, and basal secretion of surfactant lipids and proteins, suggest a significant derangement of surfactant metabolism. The phenotypic heterogeneity in infants with CAP raises the possibility that variable degrees of SP-B deficiency may be more common than previously suspected.

AB - Congenital alveolar proteinosis (CAP) is an often fatal cause af respiratory failure in term newborn infants, which has been associated with a genetic deficiency of surfactant protein B (SP-B) as a result of a frameshift mutation (121ins2) in a family with three affected siblings. In the index cases the deficiency of SP-B was associated with qualitative and quantitative abnormalities of the surfactant proteins A and C. Immunostaining for lung surfactant proteins and a search for the 121ins2 mutation by restriction enzyme analysis of DNA extracted from paraffin-embedded lung tissue was performed for 7 additional affected infants from 6 families, bringing to 10 the total number of patients with CAP who have been studied. In six infants, the surfactant protein immunostaining pattern was similar to that of the index cases. Of these, three patients were homozygous for the 121ins2 mutation; one was a compound heterozygote with the 121ins2 in one allele and a different mutation in the other; and three patients lacked the mutation in both alleles. One infant had an abundance of SP-B, suggesting phenotypic heterogeneity in CAP. Lung ultrastructural abnormalities, such as a reduced number of lamellar bodies, absent tubular myelin, and basal secretion of surfactant lipids and proteins, suggest a significant derangement of surfactant metabolism. The phenotypic heterogeneity in infants with CAP raises the possibility that variable degrees of SP-B deficiency may be more common than previously suspected.

UR - http://www.scopus.com/inward/record.url?scp=0028357903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028357903&partnerID=8YFLogxK

U2 - 10.1016/S0022-3476(94)70119-9

DO - 10.1016/S0022-3476(94)70119-9

M3 - Article

C2 - 8021783

AN - SCOPUS:0028357903

VL - 125

SP - 43

EP - 50

JO - Journal of Pediatrics

JF - Journal of Pediatrics

SN - 0022-3476

IS - 1

ER -