Clinical Characteristics And A Novel SLC34A2 Gene Mutation In A Chinese Family With Pulmonary Alveolar Microlithiasis

Backgroud pulmonary alveolar microlithiasis(PAM) is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. The onset of PAM varies from the neonatal period to old age, and the diagnosis is incidental to clinical investigations unrelated to PAM since Patients are symptom free in more than half the cases.patients with symptoms may complain of nonproductive cough, exertional dyspnea and paroxysmal hemoptysis. At most time, the progression of the disease is generally very slow. The chest X-ray typically shows diffuse micronodular shadows that are described as sand storm or snowy storm lung.Calcium stones in sputum and microliths in brochoalveolar lavage fluid or Lung biopsy can confirm PAM.PAM has been considered to be an autosomal recessive disorder, because it transmits orizontally and inbreeding frequently coexists.The etiology remained unknown until the specific gene responsible for the disease as SLC34A2 was identified in 2006, which located at a region of 4p15.31-15.2. SLC34A2, highly expressed in the lung and encoding the Sodium-dependent phosphate transport protein 2B (NaPi-IIb), is a member of the solute carrier family SLC34 that plays a major role in the homeostasis of inorganic phosphate. Dysfunction of SLC34A2 may reduce the clearance ofphosphate and may lead to the formation of microliths. Lack of clinical recognition may lead to misdiagnosis and inappropriate treatment since PAM is a rare disorder,meanwhile,there is no demostic report of seccessful PAM gene mutation research to date.Objective To investigate the clinical characteristic and mutation of SLC34A2 gene in a Chinese family with pulmonary alveolar microlithiasis.Method Clinical data of a Chinese PAM family was collected and analyzed, then DNA samples from some members of the family were screened for mutation in slc34a2 gene by Polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) and DNA sequencing.Results In this family, two Patients are still alive,including the proband and her eldest brother. They complaints of backache, cough, exertional dyspnea or paroxysmal hemoptysis. The chest X-ray typically shows diffuse micronodular shadows that are described as "sandstorm-appearing", and such microliths look like flame or white line in chest ct scan.In both alive patients of the family, a homozygous mutation of the SLC34A2 gene was identified in exon 8 (c.910A>T), creating a premature stop codon.In addition, a homozygous single nucleotide polymorphism (SNP) was found in intron 2 in such patients and the proband' s daughter.Conclusion 1. The patients we study in the family present as a autosomal recessive inheritance disease, and it is accordance with the characteristics of PAM, namely the dissociation between definite X-ray pattern of lungs and relative poor clinical symptoms.2.A novel homozygous mutation in SLC34A2 gene (c.910A>T), leading to a premature stop codon and then truncated protein,is probably responsible for PAM in this family.3.The meaning of the SNP in intron 2 remains uncertain and needs further study.