Eight novel variants in the SLC34A2 gene in pulmonary alveolar microlithiasis

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  • Åsa Lina M. Jönsson
  • Elisabeth Bendstrup
  • Susie Mogensen
  • Elizabeth J. Kopras, University of Cincinnati
  • ,
  • Francis X. McCormack, University of Cincinnati
  • ,
  • Ilaria Campo, IRCCS Policlinico S. Matteo Foundation
  • ,
  • Francesca Mariani, IRCCS Policlinico S. Matteo Foundation
  • ,
  • Amparo Escribano-Montaner, University of Valencia
  • ,
  • Are M. Holm, Oslo University Hospital
  • ,
  • Maria Del Mar Martinez-Colls, Hospital Universitari Germans Trias i Pujol
  • ,
  • Guillem Pintos-Morell, Hospital Universitari Germans Trias i Pujol, Vall d'Hebron University Hospital, Autonomous University of Barcelona
  • ,
  • Camille Taillé, Universite Paris 7
  • ,
  • Bruno Crestani, Universite Paris 7
  • ,
  • Ole Hilberg, Vejle Hospital
  • ,
  • Jane Hvarregaard Christensen
  • Ulf Simonsen

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.

Original languageEnglish
Article number1900806
JournalThe European Respiratory Journal
Number of pages11
Publication statusPublished - Feb 2020

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