Eight novel variants in the SLC34A2 gene in pulmonary alveolar microlithiasis
Por:
Jonsson, ALM, Bendstrup, E, Mogensen, S, Kopras, EJ, McCormack, FX, Campo, I, Mariani, F, Escribano-Montaner, A, Holm, AM, Martinez-Colls, MD, Pintos-Morell, G, Taille, C, Crestani, B, Hilberg, O, Christensen, JH and Simonsen, U
Publicada:
1 feb 2020
Ahead of Print:
27 feb 2020
Resumen:
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.
Filiaciones:
Jonsson, ALM:
Aarhus Univ, Dept Biomed, Bartholins Alle 6,Bldg 1242,3rd Floor, DK-8000 Aarhus C, Denmark
Bendstrup, E:
Aarhus Univ Hosp, Dept Resp Dis & Allergy, Aarhus, Denmark
Mogensen, S:
Aarhus Univ, Dept Biomed, Bartholins Alle 6,Bldg 1242,3rd Floor, DK-8000 Aarhus C, Denmark
Kopras, EJ:
Univ Cincinnati, Div Pulm Crit Care & Sleep Med, Cincinnati, OH USA
McCormack, FX:
Univ Cincinnati, Div Pulm Crit Care & Sleep Med, Cincinnati, OH USA
Campo, I:
IRCCS San Matteo Hosp Fdn, Pneumol Unit, Pavia, Italy
Mariani, F:
IRCCS San Matteo Hosp Fdn, Pneumol Unit, Pavia, Italy
Escribano-Montaner, A:
Univ Valencia, Clin Univ Hosp, Dept Pediat, Pediat Pneumol Unit, Valencia, Spain
Holm, AM:
Oslo Univ Hosp, Dept Resp Med, Oslo, Norway
Martinez-Colls, MD:
Univ Hosp Germans Trias & Pujol, Dept Pediat, Badalona, Spain
:
Univ Hosp Germans Trias & Pujol, Dept Pediat, Badalona, Spain
Univ Hosp Vall dHebron, Ctr Rare Dis, Barcelona, Spain
Univ Autonoma Barcelona, Res Inst IGTP, CIBERER GCV08, Barcelona, Spain
Taille, C:
Univ Paris Diderot, Reference Ctr Rare Pulm Dis, Hop Bichat, AP HP,Pulmonol Dept,Unite Inserm 1152,DHU FIRE, Paris, France
Crestani, B:
Univ Paris Diderot, Reference Ctr Rare Pulm Dis, Hop Bichat, AP HP,Pulmonol Dept,Unite Inserm 1152,DHU FIRE, Paris, France
Hilberg, O:
Aarhus Univ Hosp, Dept Resp Dis & Allergy, Aarhus, Denmark
Vejle Hosp, Med Dept, Vejle, Denmark
Christensen, JH:
Aarhus Univ, Dept Biomed, Bartholins Alle 6,Bldg 1242,3rd Floor, DK-8000 Aarhus C, Denmark
Simonsen, U:
Aarhus Univ, Dept Biomed, Bartholins Alle 6,Bldg 1242,3rd Floor, DK-8000 Aarhus C, Denmark
Green Published, Bronze
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