Genetic basis for childhood interstitial lung disease among Japanese infants and children

Hayasaka, Ichirô; Cho, Kazutoshi; Akimoto, Takuma; Ikeda, Masahiko; Uzuki, Yutaka; Yamada, Masafumi; Nakata, Koh; Furuta, Itsuko; Ariga, Tadashi; Minakami, Hisanori

doi:10.1038/pr.2017.217

Cited by 23 publications

(17 citation statements)

References 39 publications

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“…However, reduced transcription of SFTPC due to promotor variant were associated with neonatal respiratory distress syndrome in late preterm infants (Wambach et al, 2010) and SP-C was absent in BALF samples of a family with chronic ILDs, together with reduced pro-SP-C staining, though no mutation was identified (Amin et al, 2001). While the majority of mutations leads to the onset of ILDs already in childhood (Chibbar et al, 2004;Hamvas et al, 2004;Tredano et al, 2004;Rosen and Waltz, 2005;Stevens et al, 2005;Bullard and Nogee, 2007;Guillot et al, 2009;Mechri et al, 2010;Citti et al, 2013;Henderson et al, 2013;Hepping et al, 2013;Turcu et al, 2013;Akimoto et al, 2014;Avital et al, 2014;van Hoorn et al, 2014;Kroner et al, 2015;Liptzin et al, 2015;Peca et al, 2015;Griese et al, 2016;Liu et al, 2016;Hayasaka et al, 2018) a subset of variants results in a manifestation in later childor adulthood (Lawson et al, 2004;Setoguchi et al, 2006;Markart et al, 2007;van Moorsel et al, 2010;Ono et al, 2011;Kuse et al, 2013) suggesting a chronic process.…”

Section: Sp-c Mutations In Human Patientsmentioning

confidence: 99%

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Treumann

Baumjohann

2020

Front. Physiol.

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Sehlmeyer et al. SP-C/Cholesterol Relationships in Alveoli diffusion through lipid membranes is not well understood. However, it has been proposed that the interactions between cholesterol and the acyl carbon chains in phospholipids (stabilized by Van der Waals' forces) (Wennberg et al., 2012) create tightly packed arrangements that limits small molecule diffusion (Zocher et al., 2013). By decreasing trans-gauche rotation of the phospholipid acyl chains, membrane rigidity increases (Cassera et al., 2002; Molugu and Brown, 2019) leading to less free volume and free pockets which may accommodate oxygen, therefore reducing its flux (its partition and diffusion) through membranes (Zuniga-Hertz and Patel, 2019). Mammals developed sophisticated organs to optimize the uptake of oxygen during the life essential breathing cycle. From conducting airways to the second biggest surface exposed to the environment, the alveolar human surface (Ochs et al., 2004). In addition, the first membrane that oxygen encounters in the mammalian lungs is a complex mixture of lipids (mainly phosphatidylcholines (PC), such as dipalmitoylphosphatidylcholine (DPPC), up to a 90%) and proteins (10%) with a 5-10% of cholesterol (14-20% mol) (Zuo et al., 2008; Bernhard, 2016), called lung surfactant (surface active agent). Interestingly two surfaces in the human body present with abnormally higher cholesterol molar ratio, and both of them are in contact with the environment tightly regulating the uptake of oxygen. On the one hand, as previously explained, lung surfactant presents around a 14-20% mol cholesterol in its composition. On the other hand the eye lens surface contains up to 35% mol of cholesterol (Raguz et al., 2008; Mainali et al., 2013), compared to a normal cell plasma membrane with a 0.5 phospholipid to cholesterol molar ratio (van Meer et al., 2008; Widomska et al., 2017). Although the main function of lung Abbreviations: α-SMA, alpha smooth muscle actin; aaAMs, alternatively activated alveolar macrophages; ABCA1, ATP binding cassette transporter A1; ABCG1, ATP binding cassette transporter G1; ADA, adenosine-deaminase; ADP, adenosine diphosphate; AEC, alveolar epithelial cell; AE1C, alveolar epithelial type 1 cell; AE2C, alveolar epithelial type 2 cell; ALI

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Section: Sp-c Mutations In Human Patientsmentioning

confidence: 99%

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Treumann

Baumjohann

2020

Front. Physiol.

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“…Studies conducted in Asian countries indicated ABCA3 deficiency may indeed be rare, compared to SP‐C deficiency. A prospective cohort including neonatal patients conducted in Japan found that, of 62 chILD, 6 cases with SP‐C deficiency and none ABCA3 were identified . It is possible that the variants of genetic background may be responsible for the differences.…”

Section: Discussionmentioning

confidence: 99%

“…A prospective cohort including neonatal patients conducted in Japan found that, of 62 chILD, 6 cases with SP-C deficiency and none ABCA3 were identified. 18,19 It is possible that the variants of genetic background may be responsible for the differences. A population-based frequency of surfactant dysfunction mutations in a native Chinese cohort indicated that the collapsed carrier rate of deleterious ABCA3 mutations were 1.3%, significantly less than that of 3% to 5% reported previously in cohorts of European or African descent in the United States.…”

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confidence: 99%

Genetic basis of surfactant dysfunction in Chinese children: A retrospective study

Nong

Liu

et al. 2019

Pediatric Pulmonology

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Objective To investigate the prevalence of surfactant dysfunction (SD) and the genotype distribution in Chinese childhood interstitial lung disease (chILD). Methods From December 2013 to December 2016, whole exons and splicing regions of surfactant protein (SP)‐B, SP‐C, and adenosine triphosphate (ATP)‐binding cassette subfamily A member 3 (ABCA3) were sequenced in chILD with unknown etiology in five children's medical centers of China. The sequencing was performed by Next‐generation sequencing technique in a molecular genetics laboratory. The clinical and genetic data were reviewed retrospectively. Results In total, 136 patients of age 3 months to 13 years (mean 12.5 ± 9.4 months) were recruited, among which 76 were males. Of the 136 cases of chILD, 13.2% (18 of 136) were diagnosed with SD. In these 18 SD cases, 15 had heterozygous SP‐C deficiencies, two cases had compound heterozygous ABCA3 deficiencies, and no SP‐B deficiency was identified. In SP‐C deficiencies, there were six cases with p.I73T, 2 with p.I73N, 5 with p.V39L, 1 with c.417delA, and 1 case with IVS4, +1G>C. Two cases of ABCA3 mutation were heterozygous with c.1755delC and c.2890G>A; c.3913T>C (R1305W) and exon 13 to 18 deletion. One was negative by sequencing while diagnosed positive by pathology. Conclusion The proportion of genetic mutation of SD in chILD is 13.2% in China, of which SP‐C deficiency is predominant. The mutation, SP‐C p.V39L, was found to be relatively prevalent in China and warrants further investigation.

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“…Comparing the results of multiple studies shows that involvement of the recessive genes SFTPB and ABCA3 differs between populations [16,[35][36][37][114][115][116][117][118][119]. Furthermore, next to clinical differences between the studied cohorts, the background frequency of deleterious recessive alleles also differs between populations.…”

Section: Mutation Spectrummentioning

confidence: 99%

Genetic disorders of the surfactant system: focus on adult disease

2021

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Genes involved in the production of pulmonary surfactant are crucial for the development and maintenance of healthy lungs. Germline mutations in surfactant-related genes cause a spectrum of severe monogenic pulmonary diseases in patients of all ages. The majority of affected patients present at a very young age, however, a considerable portion of patients have adult-onset disease. Mutations in surfactant-related genes are present in up to 8% of adult patients with familial interstitial lung disease (ILD) and associate with the development of pulmonary fibrosis and lung cancer.High disease penetrance and variable expressivity underscore the potential value of genetic analysis for diagnostic purposes. However, scarce genotype–phenotype correlations and insufficient knowledge of mutation-specific pathogenic processes hamper the development of mutation-specific treatment options.This article describes the genetic origin of surfactant-related lung disease and presents spectra for gene, age, sex and pulmonary phenotype of adult carriers of germline mutations in surfactant-related genes.

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Genetic basis for childhood interstitial lung disease among Japanese infants and children

Cited by 23 publications

References 39 publications

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Genetic basis of surfactant dysfunction in Chinese children: A retrospective study

Genetic disorders of the surfactant system: focus on adult disease

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