A novel SLC34A2 mutation in a patient with pulmonary alveolar microlithiasis

Izumi, Hiroki; Kurai, Jun; Kodani, Masahiro; Watanabe, Masanari; Yamamoto, Akihiro; Nanba, Eiji; Adachi, Kaori; Igishi, Tadashi; Shimizu, Eiji

doi:10.1038/hgv.2016.47

Cited by 22 publications

(19 citation statements)

References 15 publications

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“…The SLC34A2 gene is expressed only in type II alveolar epithelium cells in the lungs ( 8 ), the main component of pulmonary surfactant produced by type II alveolar epithelial cells is dipalmitoyl lecithin. Phosphate is an important component of phospholipids, phosphate released by degraded phospholipids can be transported to the cells by NaPi-Ib in the form of NaH 2 PO 4 in the presence of sodium ions, that is alveolar phosphorus metabolism depends mainly on the normal function of NaPi-Ib ( 9 , 10 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of SLC34A2 gene mutation on extracellular phosphorus transport in PAM alveolar epithelial cells

Yan

et al. 2017

Exp Ther Med

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A mutation in the IIb sodium phosphate transporter SLC34A2 gene has recently been described in pulmonary alveolar microlithiasis (PAM) patients. Experiments in this study were aimed at confirming the role of the gene product in PAM by comparing phosphorylated products in extracellular fluid of alveolar epithelial cells overexpressing the SLC34A2 gene or its mutated version. Eukaryotic expression vectors were constructed and transfected into A549 human alveolar epithelial cells. There were three groups of cells including those transfected with empty vector plasmid pcDNA3.1(+) (plasmid control group), those transfected with normal SLC34A2 gene expressed from pcDNA3.1 (normal control group), and those transfected with a version of the PAM SLC34A2 gene linked to the pcDNA3.1(+) (PAM group). Transfection efficiencies were detected by reverse transcription-polymerase chain reaction (RT-PCR). At 48 h after transfection, the concentration of inorganic phosphorus in the culture medium was detected using an automatic biochemical analyzer. Our results showed the concentration of inorganic phosphorus in the supernatant of the normal control group was significantly lower than that in the plasmid control and PAM groups (P<0.01), and the concentration in the PAM group was significantly lower than that in the plasmid control group (P<0.01). Based on our findings it is possible that the SLC34A2 gene mutation is the cause of the pathogenic changes observed in PAM patients, given that the function of the phosphate transporter seems to be affected and it is conceivable that it would lead to extracellular fluid alterations in vivo.

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Section: Discussionmentioning

confidence: 99%

Effect of SLC34A2 gene mutation on extracellular phosphorus transport in PAM alveolar epithelial cells

Yan

et al. 2017

Exp Ther Med

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“…In a few patients, heterozygous mutations were linked to testicular microlithiasis but this has not been replicated by independent studies [15]. At present, 20 distinct mutations have been reported, including deletions, frame shifts, missense mutations as well as changes in potential splice sites and in the promoter region [15,98,37,40,89,42,102,106,20,66,75,39].…”

Section: Human Disease Associated With Napi-iib (Slc34a2) Mutationsmentioning

confidence: 99%

Clinical aspects of the phosphate transporters NaPi-IIa and NaPi-IIb: mutations and disease associations

Lederer

Wagner

2018

Pflugers Arch - Eur J Physiol

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The Na-dependent phosphate transporter NaPi-IIa (SLC34A1) is mostly expressed in kidney, whereas NaPi-IIb (SLC34A2) has a wider tissue distribution with prominent expression in the lung and small intestine. NaPi-IIa is involved in renal reabsorption of inorganic phosphate (Pi) from urine, and patients with biallelic inactivating mutations in SLC34A1 develop hypophosphatemia, hypercalcemia, hypercalciuria and nephrocalcinosis, and nephrolithiasis in early childhood. Monoallelic mutations are frequent in the general population and may impact on the risk to develop kidney stones in adulthood. SNPs in close vicinity to the SLC34A1 locus associate with the risk to develop CKD. NaPi-IIb mediates high-affinity transport of Pi from the diet and appears to be mostly important during low Pi availability. Biallelic inactivating SLC34A2 mutations are found in patients with pulmonary alveolar microlithiasis, a lung disease characterized by the deposition of microcrystals. In contrast, no evidence for disturbed systemic Pi homeostasis has been reported in these patients to date. Nevertheless, NaPi-IIb-mediated intestinal Pi absorption may be a target for pharmaceutical interventions in patients with chronic kidney disease and Pi overload.

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“…HRCT shows diffuse micronodular calcified densities with thickening of the septa 3. Other diagnostic modalities are BAL, nuclear scan, lung biopsy and detection of SLC34A2 mutation, which can help to establish the diagnosis 2 4. Military TB, sarcoidosis, histoplasmosis, and idiopathic pulmonary haemorrhage are the close differential for PAM.…”

Section: Descriptionmentioning

confidence: 99%