Neonatal respiratory failure due to novel compound heterozygous mutations in the ABCA3 lipid transporter

Zoltán N. Oltvai; Eric A. Smith; Katie Wiens; Lawrence M. Nogee; Mark Luquette; Andrew C. Nelson; Kathryn A. Wikenheiser-Brokamp

doi:10.1101/mcs.a005074

Neonatal respiratory failure due to novel compound heterozygous mutations in the ABCA3 lipid transporter

Zoltán N. Oltvai, Eric A. Smith, Katie Wiens, Lawrence M. Nogee, Mark Luquette, Andrew C. Nelson, Kathryn A. Wikenheiser-Brokamp

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

The ATP-binding cassette transporter member A3 (ABCA3) is a lipid transporter with a critical function in pulmonary surfactant biogenesis. Biallelic loss-of-function mutations in ABCA3 result in severe surfactant deficiency leading to neonatal respiratory failure with death in the first year of life. Herein, we describe a newborn with severe respiratory distress at birth progressing to respiratory failure requiring transplant. This patient was found to have a maternally inherited frameshift loss-of-function ABCA3 mutation and a paternally inherited synonymous variant in ABCA3 predicted to create a cryptic splice site. Additional studies showed reduced ABCA3 expression in hyperplastic alveolar epithelial type II cells and lamellar body alterations characteristic of ABCA3 deficiency, leading to a diagnosis of autosomal recessive ABCA3-related pulmonary surfactant dysfunction. This case highlights the need for an integrated, comprehensive approach for the diagnosis of inherited diseases when in silico modeling is utilized in the interpretation of key novel genetic mutations.

Original language	English (US)
Article number	a005074
Journal	Cold Spring Harbor Molecular Case Studies
Volume	6
Issue number	3
DOIs	https://doi.org/10.1101/mcs.a005074
State	Published - Jun 1 2020

Bibliographical note

Funding Information:
We thank the family for allowing us to publish their case. The control nontransplanted donor lung was obtained from LifeCenter Organ Donor Network (Cincinnati, OH) in collaboration with Francis X. McCormack, MD (University of Cincinnati, Cincinnati, OH). This study was also supported by services from the Pathology Research Core shared facility in the Cincinnati Children’s Research Foundation with specific acknowledgment of the assistance of Robin Sams.

Publisher Copyright:
© 2020 Oltvai et al. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.

Keywords

cyanosis
progressive pulmonary function impairment
respiratory insufficiency

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't
Case Reports

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1101/mcs.a005074

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abstract = "The ATP-binding cassette transporter member A3 (ABCA3) is a lipid transporter with a critical function in pulmonary surfactant biogenesis. Biallelic loss-of-function mutations in ABCA3 result in severe surfactant deficiency leading to neonatal respiratory failure with death in the first year of life. Herein, we describe a newborn with severe respiratory distress at birth progressing to respiratory failure requiring transplant. This patient was found to have a maternally inherited frameshift loss-of-function ABCA3 mutation and a paternally inherited synonymous variant in ABCA3 predicted to create a cryptic splice site. Additional studies showed reduced ABCA3 expression in hyperplastic alveolar epithelial type II cells and lamellar body alterations characteristic of ABCA3 deficiency, leading to a diagnosis of autosomal recessive ABCA3-related pulmonary surfactant dysfunction. This case highlights the need for an integrated, comprehensive approach for the diagnosis of inherited diseases when in silico modeling is utilized in the interpretation of key novel genetic mutations.",

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note = "Funding Information: We thank the family for allowing us to publish their case. The control nontransplanted donor lung was obtained from LifeCenter Organ Donor Network (Cincinnati, OH) in collaboration with Francis X. McCormack, MD (University of Cincinnati, Cincinnati, OH). This study was also supported by services from the Pathology Research Core shared facility in the Cincinnati Children{\textquoteright}s Research Foundation with specific acknowledgment of the assistance of Robin Sams. Publisher Copyright: {\textcopyright} 2020 Oltvai et al. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.",

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Neonatal respiratory failure due to novel compound heterozygous mutations in the ABCA3 lipid transporter

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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