Case of familial interstitial lung disease attributed to ATP-binding cassette transporter 3 gene mutation in identical twins

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Kazuo Tsuchiya
Yutaro Nakamura
Yasuhiro Setoguchi
Sayomi Matsushima
Moriya Iwaizumi
Yusuke Inoue
Hideki Yasui
Hironao Hozumi
Masato Karayama
Yuzo Suzuki
Kazuki Furuhashi
Noriyuki Enomoto
Tomoyuki Fujisawa
Naoki Inui
Takafumi Suda

Keywords

ABCA3 mutation, identical twins, interstitial lung disease

Abstract

Mutations in ABCA3 can result in surfactant deficiency, leading to respiratory distress syndrome in term neonates, and interstitial lung disease (ILD) in children. Here, we report an extremely rare case of ILD in an identical twin with novel ABCA3 germline mutations. Interestingly, they showed mostly similar, but slightly different, clinical features. Our cases suggest that, in addition to genetic factors, non-genetic factors are involved in the severity of the disease and its clinical course. Studies of gene-environment interactions, especially with twins, are needed, as they may contribute to the understanding of the clinical heterogeneity of ILD and its 
association with various underlying conditions as well as rare variant mutations.

Abstract 118 | PDF Downloads 131

References

1. Beers MF, Mulugeta S. The biology of the ABCA3 lipid transporter in lung health and disease. Cell Tissue Res. 2017;367:481-493.
2. Singh J, Jaffe A, Schultz A, Selvadurai H. Surfactant protein disorders in childhood interstitial lung disease. Eur J Pediatr. 2021;180:2711-2721.
3. Nathan N, Berdah L, Delestrain C, Sileo C, Clement A. Interstitial lung diseases in children. Presse Med. 2020;49:103909.
4. Legendre M, Darde X, Ferreira M, et al. The clinical course of interstitial lung disease in an adult patient with an ABCA3 homozygous complex allele under hydroxychloroquine and a review of the literature. Sarcoidosis Vasc Diffuse Lung Dis. 2022;39:e2022019.
5. Wang J, Fan J, Zhang Y, Huang L, Shi Y. ABCA3 gene mutations shape the clinical profiles of severe unexplained respiratory distress syndrome in late preterm and term infants. Transl Pediatr. 2021;10:350-358.
6. Zhang W, Liu Z, Lin Y, et al. A novel synonymous ABCA3 variant identified in a Chinese family with lethal neonatal respiratory failure. BMC Med Genomics. 2021;14:256.
7. Chan KJ, Thong MK, Nathan AM, Thavagnanam S, Yakob Y, Gan CS. Childhood interstitial lung disease: The end of a diagnostic odyssey. Ann Acad Med Singap. 2022;51:651-652.
8. Jouza M, Jimramovsky T, Sloukova E, et al. A Newly Observed Mutation of the ABCA3 Gene Causing Lethal Respiratory Failure of a Full-Term Newborn: A Case Report. Front Genet. 2020;11:568303.
9. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-424.
10. Denman L, Yonker LM, Kinane TB. The classification of ATP-binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system. Pediatr Investig. 2018;2:17-24.
11. Klay D, Platenburg M, van Rijswijk R, Grutters JC, van Moorsel CHM. ABCA3 mutations in adult pulmonary fibrosis patients: a case series and review of literature. Current opinion in pulmonary medicine. 2020;26:293-301.
12. Kaltenborn E, Kern S, Frixel S, et al. Respiratory syncytial virus potentiates ABCA3 mutation-induced loss of lung epithelial cell differentiation. Hum Mol Genet. 2012;21:2793-2806.
13. Marciniak SJ. Endoplasmic reticulum stress in lung disease. Eur Respir Rev. 2017;26:170018.