case_images: PMC9019779_01
case_images: Chest X-ray and high-resolution computed tomography (HRCT) scan findings in two patients. (A) Chest X-ray revealed multiple patchy shadows in both lung fields of patient 1 at 60 days of age (P1). The chest HRCT of the patient showed large scattered ground-glass opacity in both lung fields at 46 days of age (1a, 1b, and 1c). (B) Chest X-ray of patient2 revealed the bilateral diffuse plaque-like shadows (P2). The chest HRCT scan showed multiple striped fuzzy shadows and ground-glass opacity in both lung fields (2a, 2b, and 2c).
case_images: fgene-13-875015-g001.jpg
case_images: PMC9019779_02_fgene-13-875015-g001.jpg
case_images: F1
case_images: Chest X-ray revealed bilateral diffuse plaque-like shadows (Figure 1B). HRCT scan showed multiple striped fuzzy shadows and ground-glass opacity in both lung fields (Figure 1B, 2a-c). His parents were both asymptomatic, and no family history of genetic disease was reported.
case_images: Sanger sequencing confirmation of the ABCA3 gene variants detected by exome sequencing. (A) The highlighting blue background area showed two heterozygous paternally inherited variants (c.4035+5G > A; c.668T > C, p.M223T) and a heterozygous maternally inherited variant (c.1285+4A > C) in ABCA3 gene in patient 1. (B) Patient 2 had a heterozygous missense variant c.704T > C (p.F235S) inherited from the father and a heterozygous frameshift variant c.4037_4040del (p.T1346Nfs*15) from the mother in the ABCA3 gene. Sanger sequencing showed the antisense sequence alignment of the ABCA3 gene.
case_images: fgene-13-875015-g002.jpg
case_images: PMC9019779_02_fgene-13-875015-g002.jpg
case_images: F2
case_images: HRCT scan showed multiple striped fuzzy shadows and ground-glass opacity in both lung fields (Figure 1B, 2a-c). His parents were both asymptomatic, and no family history of genetic disease was reported. The genetic analysis showed compound heterozygous ABCA3 variants; paternally inherited c.704T > C (p.F235S) in exon 8, and maternally inherited c.4037_4040del (p.T1346Nfs*15) in exon 27 (Figure 2B).
case_images: Schematic representation of missense variants p.M223T and p. F235S on the ABCA3 protein. (A) Predicted tertiary structure of the ABCA3 transporter by PyMOL. ABCA3 is an integral membrane protein that contains 12 membrane-spanning helices and two cytosolic nucleotide binding domains. The two missense variants were located on the extracellular domain. (B) Spatial disposition of the amino acid residues Met223, Leu1065, and Phe1062. (C) Spatial disposition of the amino acid residues Phe235, Arg220, and Leu1061.
case_images: fgene-13-875015-g003.jpg
case_images: PMC9019779_02_fgene-13-875015-g003.jpg
case_images: F3
case_images: The predicted tertiary structure of the ABCA3 transporter showed the location of the missense variant p.M223T (Figure 3), and the variant was predicted to be deleterious by different algorithms (SIFT: 0.001, Damaging; Polyphen-2: 0.744, Probably_damaging; MutationTaster: 1.000, Disease_causing; FATHMM: 4.28, Damaging; and CADD: 21.0, Damaging).
case_images: PMC9019779_02
case_images: Chest X-ray and high-resolution computed tomography (HRCT) scan findings in two patients. (A) Chest X-ray revealed multiple patchy shadows in both lung fields of patient 1 at 60 days of age (P1). The chest HRCT of the patient showed large scattered ground-glass opacity in both lung fields at 46 days of age (1a, 1b, and 1c). (B) Chest X-ray of patient2 revealed the bilateral diffuse plaque-like shadows (P2). The chest HRCT scan showed multiple striped fuzzy shadows and ground-glass opacity in both lung fields (2a, 2b, and 2c).
case_images: fgene-13-875015-g001.jpg
case_images: PMC9019779_02_fgene-13-875015-g001.jpg
case_images: F1
case_images: Chest X-ray revealed bilateral diffuse plaque-like shadows (Figure 1B). HRCT scan showed multiple striped fuzzy shadows and ground-glass opacity in both lung fields (Figure 1B, 2a-c). His parents were both asymptomatic, and no family history of genetic disease was reported.
case_images: Sanger sequencing confirmation of the ABCA3 gene variants detected by exome sequencing. (A) The highlighting blue background area showed two heterozygous paternally inherited variants (c.4035+5G > A; c.668T > C, p.M223T) and a heterozygous maternally inherited variant (c.1285+4A > C) in ABCA3 gene in patient 1. (B) Patient 2 had a heterozygous missense variant c.704T > C (p.F235S) inherited from the father and a heterozygous frameshift variant c.4037_4040del (p.T1346Nfs*15) from the mother in the ABCA3 gene. Sanger sequencing showed the antisense sequence alignment of the ABCA3 gene.
case_images: fgene-13-875015-g002.jpg
case_images: PMC9019779_02_fgene-13-875015-g002.jpg
case_images: F2
case_images: HRCT scan showed multiple striped fuzzy shadows and ground-glass opacity in both lung fields (Figure 1B, 2a-c). His parents were both asymptomatic, and no family history of genetic disease was reported. The genetic analysis showed compound heterozygous ABCA3 variants; paternally inherited c.704T > C (p.F235S) in exon 8, and maternally inherited c.4037_4040del (p.T1346Nfs*15) in exon 27 (Figure 2B).
case_images: Schematic representation of missense variants p.M223T and p. F235S on the ABCA3 protein. (A) Predicted tertiary structure of the ABCA3 transporter by PyMOL. ABCA3 is an integral membrane protein that contains 12 membrane-spanning helices and two cytosolic nucleotide binding domains. The two missense variants were located on the extracellular domain. (B) Spatial disposition of the amino acid residues Met223, Leu1065, and Phe1062. (C) Spatial disposition of the amino acid residues Phe235, Arg220, and Leu1061.
case_images: fgene-13-875015-g003.jpg
case_images: PMC9019779_02_fgene-13-875015-g003.jpg
case_images: F3
case_images: The predicted tertiary structure of the ABCA3 transporter showed the location of the missense variant p.M223T (Figure 3), and the variant was predicted to be deleterious by different algorithms (SIFT: 0.001, Damaging; Polyphen-2: 0.744, Probably_damaging; MutationTaster: 1.000, Disease_causing; FATHMM: 4.28, Damaging; and CADD: 21.0, Damaging).