Combined pulmonary fibrosis and emphysema syndrome associated with<i>ABCA3</i>mutations

Epaud, Ralph; Delestrain, Céline; Louha, Malek; Simon, Stéphanie; Fanen, Pascale; Tazi, Abdellatif

doi:10.1183/09031936.00145213

Cited by 73 publications

(60 citation statements)

References 10 publications

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“…Also highlighting that the prognosis is more variable for these genotypes is the finding that most infants who presented after the newborn period were alive at 1 year (72%). Some have survived into adolescence (23) and even adulthood (24). Although all siblings in our study were concordant for outcome at 1 year of age (death or transplant vs. alive) (see Tables E1 and E2), discordant outcomes between siblings have been reported (25,26).…”

Section: Discussionmentioning

confidence: 61%

“…Because 25% (34 of 136; two age of presentations unknown) of subjects with null/other and other/other genotypes presented beyond the newborn period, clinical sequencing for ABCA3 deficiency should be strongly considered for patients with less severe, but unexplained lung disease, as has been recently recommended (2013 American Thoracic Society statement) (27). Although this study did not include subjects presenting with interstitial lung disease beyond childhood, a recent report of an adult patient with ABCA3 deficiency and the increased availability of clinical ABCA3 sequencing suggests that additional cases in adults will be identified (24).…”

Section: Discussionmentioning

confidence: 99%

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Genotype–Phenotype Correlations for Infants and Children with ABCA3 Deficiency

Wambach

Casey

Fishman

et al. 2014

Am J Respir Crit Care Med

186

223

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Rationale: Recessive mutations in the ATP-binding cassette transporter A3 (ABCA3) cause lethal neonatal respiratory failure and childhood interstitial lung disease. Most ABCA3 mutations are private.Objectives: To determine genotype-phenotype correlations for recessive ABCA3 mutations.Methods: We reviewed all published and unpublished ABCA3 sequence and phenotype data from our prospective genetic studies of symptomatic infants and children at Washington and Johns Hopkins Universities. Mutations were classified based on their predicted disruption of protein function: frameshift and nonsense mutations were classified as "null," whereas missense, predicted splice site mutations, and insertion/deletions were classified as "other." We compared age of presentation and outcomes for the three genotypes: null/null, null/other, and other/other. Measurements and Main Results:We identified 185 infants and children with homozygous or compound heterozygous ABCA3 mutations and lung disease. All of the null/null infants presented with respiratory failure at birth compared with 75% of infants with null/ other or other/other genotypes (P = 0.00011). By 1 year of age, all of the null/null infants had died or undergone lung transplantation compared with 62% of the null/other and other/other children (P , 0.0001).Conclusions: Genotype-phenotype correlations exist for homozygous or compound heterozygous mutations in ABCA3. Frameshift or nonsense ABCA3 mutations are predictive of neonatal presentation and poor outcome, whereas missense, splice site, and insertion/deletions are less reliably associated with age of presentation and prognosis. Counseling and clinical decision making should acknowledge these correlations.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Genotype–Phenotype Correlations for Infants and Children with ABCA3 Deficiency

Wambach

Casey

Fishman

et al. 2014

Am J Respir Crit Care Med

186

223

View full text Add to dashboard Cite

show abstract

“…Biallelic ABCA3 mutations and heterozygous SFTPC mutations in adults may have a similar clinical and radiological presentation [83,84]. The most frequent radiological pattern associates predominant diffuse ground-glass opacities, septal thickening and cysts of variable size with a preferential distribution in the upper lobes and in subpleural areas (figure 4) [85][86][87].…”

Section: Surfactant Protein Mutationsmentioning

confidence: 99%

Management of suspected monogenic lung fibrosis in a specialised centre

et al. 2017

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At least 10% of patients with interstitial lung disease present monogenic lung fibrosis suspected on familial aggregation of pulmonary fibrosis, specific syndromes or early age of diagnosis. Approximately 25% of families have an identified mutation in genes mostly involved in telomere homeostasis, and more rarely in surfactant homeostasis.Beyond pathophysiological knowledge, detection of these mutations has practical consequence for patients. For instance, mutations involved in telomere homeostasis are associated with haematological complications after lung transplantation and may require adapted immunosuppression. Moreover, relatives may benefit from a clinical and genetic evaluation that should be specifically managed.The field of genetics of pulmonary fibrosis has made great progress in the last 10 years, raising specific problems that should be addressed by a specialised team.

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“…2 in non smokers certain mutations in surfactant related genes like ABCA3 which has a role in surfactant storage and homeostasis has been identified. 3 There has been few case reports since then and an even more few case series and even more so from India.…”

Section: Introductionmentioning

confidence: 99%