Published ahead of print on November 9, 2006, doi:10.1164/rccm.200609-1274OC Am. J. Respir. Crit. Care Med., Volume 175, Number 3, February 2007, 263-268 A more recent version of this article appeared on February 1, 2007
Submitted on September 7, 2006 Mutations in the SLC34A2 Gene are Associated with the Pulmonary Alveolar MicrolithiasisHuqun1,1 Department of Respiratory Medicine, Saitama Medical School, Saitama, Japan; Department of Respiratory Oncology and Molecular Medicine, Tohoku University, Sendai, Japan, 2 Department of Pulmonary Medicine, International Medical Center of Japan, Tokyo, Japan, 3 Department of Respiratory Medicine, Saitama Medical School, Saitama, Japan, 4 Department of Cardiovascular Pharmacology, Yamagata University, Yamagata, Japan, 5 Department of Respiratory Medicine, Katta General Hospital, Miyagi, Japan, 6 Department of Respiratory Medicine, Kurashiki Central Hospital, Okayama, Japan, 7 Department of Respiratory Medicine, Tama Hokubu Hospital, Tokyo, Japan, 8 Department of Respiratory Oncology and Molecular Medicine, Tohoku University, Sendai, Japan, 9 The Third Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan, 10 Department of Surgery II, Fukushima Medical University, Fukushima, Japan, 11 Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, Tokyo, Japan * To whom correspondence should be addressed. E-mail: hagiwark{at}saitama-med.ac.jp.
Rationale: Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space. Objectives: To identify the responsible gene that causes pulmonary alveolar microlithiasis. Methods: By a genome-wide SNP analysis using DNA from 3 patients, we have narrowed the region where the candidate gene is located. From which we have identified a gene that has mutations in all patients. Measurements and Main results: We identified a candidate gene SLC34A2 that encodes a type IIb sodium phosphate cotransporter is mutated in six of six patients investigated. SLC34A2 is specifically expressed in the type II alveolar cells, and the mutations abolished the normal gene function. Conclusion: Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis. Key words: Pulmonary alveolar microlithiasis, Homozygosity mapping, GeneChip, SNPs
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