Adult‐onset familial pulmonary fibrosis in Japanese brothers

Abstract

Two Japanese brothers were diagnosed in their 20s with familial pulmonary fibrosis, the pathological findings of which were consistent with usual interstitial pneumonia (UIP). However, an atypical characteristic was observed in the lungs of these brothers; 2-mm areas of 'honeycomb' were identified throughout the lungs, which is smaller than the generally observed 5-10 mm honeycombing seen in UIP. Fibroblastic foci were demonstrated in the second eldest brother, but not in the eldest, which indicates that the lungs of the eldest brother was in a more advanced stage of fibrosis. Their youngest brother and parents have no clinical evidence of pulmonary fibrosis. All five family members had low values for the diffusion capacity of the lung for carbon monoxide (DLCO), suggesting the presence of an inheritable disease and the existence of different phenotypes. The genomic DNA of the affected brothers was sequenced for the reported surfactant protein C (SP-C) gene mutations in patients with familial pulmonary fibrosis, but none was documented. It is necessary to clarify the presence of novel gene mutations of SP-C or other genes to explain these particular pathological findings and the low DLCO observed in this family.

A homozygous SFTPA1 mutation drives necroptosis of type II alveolar epithelial cells in patients with idiopathic pulmonary fibrosis

“…Patient history and genetic analysis In a single Japanese family with consanguineous marriage, two of the sons were diagnosed with IPF at the ages of 24 and 27 yr and died at 32 and 34 yr, respectively (Fig. S1 a; Yoshioka et al, 2004). The youngest brother also began to develop dyspnea at the age of 40 yr.…”

European Respiratory Society statement on familial pulmonary fibrosis

“…Disease penetrance in SRG mutation carriers is high and documented asymptomatic mutation carriers are rare [58]. Screening of such relatives revealed subclinical disease with below normal lung function or the presence of ILD changes on HRCT in adults [62,[130][131][132]. Little is known on asymptomatic paediatric carriers.…”

Genetic disorders of the surfactant system: focus on adult disease

“…Thereafter three other families were described, each with their own unique exon 6 SFTPA1 mutation [97][98][99], including the homozygous adult sons of consanguineous heterozygous Japanese parents [99]. The parents were asymptomatic but, upon examination, subclinical disease with a D LCO <63% predicted was detected [100].…”

“…For necroptosis, both tumour-promoting and tumour-suppressing effects are reported [128]. In the study of a family with an SFTPA1 mutation and evidence of necropsis, one uncle with lung cancer was reported; however, his mutation status was unknown and tumourigenesis was not studied [99,100]. Secondly, the expression of SP-A protein is not limited to AT2 epithelial cells but also occurs in club cells.…”