PT  - JOURNAL ARTICLE
AU  - Åsa Lina M. Jönsson
AU  - Elisabeth Bendstrup
AU  - Susie Mogensen
AU  - Elizabeth J. Kopras
AU  - Francis X. McCormack
AU  - Ilaria Campo
AU  - Francesca Mariani
AU  - Amparo Escribano-Montaner
AU  - Are M. Holm
AU  - Maria del Mar Martinez-Colls
AU  - Guillem Pintos-Morell
AU  - Camille Taillé
AU  - Bruno Crestani
AU  - Ole Hilberg
AU  - Jane Hvarregaard Christensen
AU  - Ulf Simonsen
TI  - Eight novel variants in the <em>SLC34A2</em> gene in pulmonary alveolar microlithiasis
AID  - 10.1183/13993003.00806-2019
DP  - 2020 Feb 01
TA  - European Respiratory Journal
PG  - 1900806
VI  - 55
IP  - 2
4099  - http://erj.ersjournals.com/content/55/2/1900806.short
4100  - http://erj.ersjournals.com/content/55/2/1900806.full
SO  - Eur Respir J2020 Feb 01; 55
AB  - Background Pulmonary alveolar microlithiasis (PAM) is caused by genetic variants in the SLC34A2 gene, which encodes the sodium-dependent phosphate transport protein 2B (NaPi-2b). PAM is characterised by deposition of calcium phosphate concretions (microliths) in the alveoli leading to pulmonary dysfunction. The variant spectrum of SLC34A2 has not been well investigated and it is not yet known whether a genotype–phenotype correlation exists.Methods We collected DNA from 14 patients with PAM and four relatives, and analysed the coding regions of SLC34A2 by direct DNA sequencing. To determine the phenotype characteristics, clinical data were collected and a severity score was created for each variant, based on type and localisation within the protein.Results We identified eight novel allelic variants of SLC34A2 in 14 patients with PAM. Four of these were nonsense variants, three were missense and one was a splice site variant. One patient was heterozygous for two different variants and all other patients were homozygous. Four patients were asymptomatic and 10 patients were symptomatic. The severity of the disease was associated with the variant severity.Conclusions Our findings support a significant role for SLC34A2 in PAM and expand the variant spectrum of the disease. Thus, SLC34A2 variants were detected in all patients and eight novel allelic variants were discovered. An association between disease severity and the severity of the variants was found; however, this needs to be investigated in larger patient populations.Eight novel variants in the SLC34A2 gene have been identified in 14 patients with pulmonary alveolar microlithiasis (PAM), which emphasises the importance of the gene in the disease. Furthermore, a genotype–phenotype correlation in PAM may exist. http://bit.ly/3307M1p