Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis.
BACKGROUND
Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space.


OBJECTIVE
To identify the responsible gene that causes pulmonary alveolar microlithiasis.


METHODS
By means of a genomewide single-nucleotide polymorphism analysis using DNA from three patients, we have narrowed the region in which the candidate gene is located. From this region, we have identified a gene that has mutations in all patients with pulmonary alveolar microlithiasis.


RESULTS
We identified a candidate gene, SLC34A2, that encodes a type IIb sodium phosphate cotransporter and that is mutated in six of six patients investigated. SLC34A2 is specifically expressed in type II alveolar cells, and the mutations abolished the normal gene function.


CONCLUSIONS
Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis.
Huqun
Departments of Respiratory Medicine, Pathology, and Chest Surgery, Saitama Medical University, Saitama, Japan.
Izumi
Shinyu
S
Miyazawa
Hitoshi
H
Ishii
Kuniaki
K
Uchiyama
Bine
B
Ishida
Tadashi
T
Tanaka
Sawako
S
Tazawa
Ryushi
R
Fukuyama
Shunichiro
S
Tanaka
Tomoaki
T
Nagai
Yoshiaki
Y
Yokote
Akemi
A
Takahashi
Hiroki
H
Fukushima
Toshihiko
T
Kobayashi
Kunihiko
K
Chiba
Hirofumi
H
Nagata
Makoto
M
Sakamoto
Susumu
S
Nakata
Koichiro
K
Takebayashi
Yuji
Y
Shimizu
Yoshihiko
Y
Kaneko
Koichi
K
Shimizu
Michio
M
Kanazawa
Minoru
M
Abe
Shosaku
S
Inoue
Yoshikazu
Y
Takenoshita
Seiichi
S
Yoshimura
Kunihiko
K
Kudo
Koichiro
K
Tachibana
Teruo
T
Nukiwa
Toshihiro
T
Hagiwara
Koichi
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020347:Lithiasis / Q000235:genetics* / Q000473:pathology*; D008171:Lung Diseases / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D013902:Radiography, Thoracic; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000032:analysis / Q000235:genetics*; D014982:Xenopus laevis
D012333:RNA, Messenger; C493557:SLC34A2 protein, human; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb