Genetic testing in idiopathic interstitial pneumonia

Abstract

Background: Idiopathic interstitial pneumonia (IIP)s are severe diseases that can occur from neonates to elderly. A genetic cause is identified in around 2% cases in sporadic cases, and up to 20% in familial cases, telomerase genes mutations being the first etiology. We aimed to identify the relevance of a systematic surfactant genetic testing in familial or sporadic early cases (before 50 years-old) of IIP with no telomerase gene mutations. Methods: Patients were recruited through the French national network for rare lung diseases. All the surfactant system genes in which mutations has been involved in IIP were sequenced by Sanger method: genes encoding the surfactant proteins A2, B and C ( SFTPA2 , SFTPB , SFTPC) , and their transporter, the ATP-binding cassette family A member 3 ( ABCA3 ). A signed informed consent and a clinical form were obtained for each patient. Results: A population of 227 patients (203 unrelated families) was included. Forty-two cases (20%) were familial, 89 were children at the time of the diagnosis. A genetic cause was identified for 15 unrelated patients (7.4% of the families): 7 children aged 0 to 1.5 years, and 8 adults aged 28 to 64 years, including 3 familial cases. In children, 4 had a SFTPC mutation, 3 had a homozygous or compound heterozygous ABCA3 mutation. In adults, 2 had a SFTPA2 mutation, 4 a SFTPC mutation and 2 an ABCA3 mutation. In addition, 8 patients had a heterozygous ABCA3 mutation. Discussion: A genetic cause of IIP has been identified in a number of IIP, not only in familial cases (7%), but also in sporadic cases (7%), in children (7.9%) and in adult cases (7%). These results suggest that surfactant testing is of importance in the diagnosis of IIP in children, but also in adults.