TY - JOUR
T1 - A novel germline mutation of the SFTPA1 gene in familial interstitial pneumonia
AU - Doubková, Martina
AU - Staňo Kozubík, Kateřina
AU - Radová, Lenka
AU - Pešová, Michaela
AU - Trizuljak, Jakub
AU - Pál, Karol
AU - Svobodová, Klára
AU - Réblová, Kamila
AU - Svozilová, Hana
AU - Vrzalová, Zuzana
AU - Pospíšilová, Šárka
AU - Doubek, Michael
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Different genes related to alveolar stability have been associated with familial interstitial pneumonia (FIP). Here, we report a novel, rare SFTPA1 variant in a family with idiopathic interstitial pneumonia (IIP). We performed whole-exome sequencing on germline DNA samples from four members of one family; three of them showed signs of pulmonary fibrosis (idiopathic interstitial pneumonia) with autosomal-dominant inheritance. A heterozygous single nucleotide variant c.532 G > A in the SFTPA1 gene has been identified. This variant encodes the substitution p.(Val178Met), localized within the carbohydrate recognition domain of surfactant protein A and segregates with the genes causing idiopathic interstitial pneumonia. This rare variant has not been previously reported. We also analyzed the detected sequence variant in the protein structure in silico. The replacement of valine by the larger methionine inside the protein may cause a disruption in the protein structure. The c.532 G > A variant was further validated using Sanger sequencing of the amplicons, confirming the diagnosis in all symptomatic family members. Moreover, this variant was also found by Sanger sequencing in one other symptomatic family member and one young asymptomatic family member. The autosomal-dominant inheritance, the family history of IIP, and the evidence of a mutation occurring in part of the SFTPA1 gene all suggest a novel variant that causes FIP.
AB - Different genes related to alveolar stability have been associated with familial interstitial pneumonia (FIP). Here, we report a novel, rare SFTPA1 variant in a family with idiopathic interstitial pneumonia (IIP). We performed whole-exome sequencing on germline DNA samples from four members of one family; three of them showed signs of pulmonary fibrosis (idiopathic interstitial pneumonia) with autosomal-dominant inheritance. A heterozygous single nucleotide variant c.532 G > A in the SFTPA1 gene has been identified. This variant encodes the substitution p.(Val178Met), localized within the carbohydrate recognition domain of surfactant protein A and segregates with the genes causing idiopathic interstitial pneumonia. This rare variant has not been previously reported. We also analyzed the detected sequence variant in the protein structure in silico. The replacement of valine by the larger methionine inside the protein may cause a disruption in the protein structure. The c.532 G > A variant was further validated using Sanger sequencing of the amplicons, confirming the diagnosis in all symptomatic family members. Moreover, this variant was also found by Sanger sequencing in one other symptomatic family member and one young asymptomatic family member. The autosomal-dominant inheritance, the family history of IIP, and the evidence of a mutation occurring in part of the SFTPA1 gene all suggest a novel variant that causes FIP.
UR - http://www.scopus.com/inward/record.url?scp=85069296874&partnerID=8YFLogxK
U2 - 10.1038/s41439-019-0044-z
DO - 10.1038/s41439-019-0044-z
M3 - Article
AN - SCOPUS:85069296874
SN - 2054-345X
VL - 6
JO - Human Genome Variation
JF - Human Genome Variation
IS - 1
M1 - 12
ER -