Chest
Volume 137, Issue 4, April 2010, Pages 969-973
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Selected Reports
Identification of Early Interstitial Lung Disease in an Individual With Genetic Variations in ABCA3 and SFTPC

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A man with usual interstitial pneumonia (age of onset 58 years) was previously found to have an Ile73Thr (I73T) surfactant protein C (SFTPC) mutation. Genomic DNA from the individual and two daughters (aged 39 and 43 years) was sequenced for the I73T mutation and variations in ATP-binding cassette A3 (ABCA3). All three had the I73T SFTPC mutation. The father and one daughter (aged 39 years) also had a transversion encoding an Asp123Asn (D123N) substitution in ABCA3. The daughters were evaluated by pulmonary function testing and high-resolution CT (HRCT). Neither daughter had evidence of disease, except for focal subpleural septal thickening on HRCT scan in one daughter (aged 39 years). This daughter underwent bronchoscopy with transbronchial biopsies revealing interstitial fibrotic remodeling. These findings demonstrate that subclinical fibrotic changes may be present in family members of patients with SFTPC mutation-associated interstitial lung disease and suggest that ABCA3 variants could affect disease pathogenesis.

Section snippets

Case Report

We previously reported a study in which we screened for SFTPC mutations in DNA from sporadic cases of UIP (89 patients) and nonspecific interstitial pneumonia (46 patients). In this study, only one individual out of 135 had a mutation in SFTPC, a threonine-to-isoleucine substitution in codon 73 (I73T).10 The heterozygous I73T mutation may be the most common SFTPC mutation as it has been reported in several children with ILD.11 This 61-year-old man had been diagnosed with IPF based on clinical

Discussion

In this report, we describe the presence of two heterozygous gene variations, I73T SFTPC and D123N ABCA3, within a single family. In addition, we found evidence of early ILD in an asymptomatic family member. HRCT scan of this daughter, who like her father carried both variations, demonstrated subtle interstitial changes within the lower lobes of the lungs, suggesting the presence of subclinical ILD. Transbronchial biopsies also demonstrated findings consistent with early ILD. Interestingly,

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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Funding/Support: This study was funded by the National Institutes of Health [Grants HL85317, HL85406, HL87738, M01 RR00095, and UL1 RR024975]; American Thoracic Society Research Grant Program; American Lung Association Dalsemer Research Grant; and the Francis Family Foundation. Dr Lawson is a Parker B. Francis Fellow in Pulmonary Research.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).

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