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Two novel gene mutations identified in a child with pulmonary alveolar microlithiasis complicated with bronchitis obliterans: A case report and literature review.

ABSTRACT: We reported a case of a 7-year-old boy with pulmonary alveolar microlithiasis (PAM) and detected two novel compound heterozygous mutations of solute carrier family 34 member 2 (SLC34A2), EXON:2-6 duplication and c.1218 (EXON:11) C > A (p. Phe406Leu). His symptoms were nonspecific. Chest computed tomography (CCT) showed bronchiectasis, a mosaic feature, and extensive calcifications in both lungs. In addition, bronchoscopy showed bronchitis obliterans which has rarely been reported as a complication in the literature. This case aimed to explore the mechanism of PAM and emphasize the role of gene analysis in diagnosing rare pediatric diseases. Finally, we undertook a review of the current literature containing SLC34A2 gene mutations to update the gene mutation spectrum of PAM.

SUBMITTER: Zhang M

PROVIDER: S-EPMC10415588 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Two novel gene mutations identified in a child with pulmonary alveolar microlithiasis complicated with bronchitis obliterans: A case report and literature review.

Zhang Meiyu M Gao Man M Liu Yuhuan Y Wang Kun K Zhou Siyan S Jing Haoran H Yin Guo G Meng Fanzheng F

Clinical case reports 20230810 8

We reported a case of a 7-year-old boy with pulmonary alveolar microlithiasis (PAM) and detected two novel compound heterozygous mutations of solute carrier family 34 member 2 (SLC34A2), EXON:2-6 duplication and c.1218 (EXON:11) C > A (p. Phe406Leu). His symptoms were nonspecific. Chest computed tomography (CCT) showed bronchiectasis, a mosaic feature, and extensive calcifications in both lungs. In addition, bronchoscopy showed bronchitis obliterans which has rarely been reported as a complicati ...[more]

PMID: 37575464

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Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis.

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Impaired phosphate transport in SLC34A2 variants in patients with pulmonary alveolar microlithiasis.

Project description:BackgroundVariants in SLC34A2 encoding the sodium-dependent phosphate transport protein 2b (NaPi-IIb) cause the rare lung disease pulmonary alveolar microlithiasis (PAM). PAM is characterised by the deposition of calcium-phosphate concretions in the alveoli usually progressing over time. No effective treatment is available. So far, 30 allelic variants in patients have been reported but only a few have been functionally characterised. This study aimed to determine the impact of selected SLC34A2 variants on transporter expression and phosphate uptake in cellular studies.MethodsTwo nonsense variants (c.910A > T and c.1456C > T), one frameshift (c.1328delT), and one in-frame deletion (c.1402_1404delACC) previously reported in patients with PAM were selected for investigation. Wild-type and mutant c-Myc-tagged human NaPi-IIb constructs were expressed in Xenopus laevis oocytes. The transport function was investigated with a 32Pi uptake assay. NaPi-IIb protein expression and localisation were determined with immunoblotting and immunohistochemistry, respectively.ResultsOocytes injected with the wild-type human NaPi-IIb construct had significant 32Pi transport compared to water-injected oocytes. In addition, the protein had a molecular weight as expected for the glycosylated form, and it was readily detectable in the oocyte membrane. Although the protein from the Thr468del construct was synthesised and expressed in the oocyte membrane, phosphate transport was similar to non-injected control oocytes. All other mutants were non-functional and not expressed in the membrane, consistent with the expected impact of the truncations caused by premature stop codons.ConclusionsOf four analysed SLC34A2 variants, only the Thr468del showed similar protein expression as the wild-type cotransporter in the oocyte membrane. All mutant transporters were non-functional, supporting that dysfunction of NaPi-IIb underlies the pathology of PAM.

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