Dataset Information

SLC34A2 gene compound heterozygous mutation identification in a patient with pulmonary alveolar microlithiasis and computational 3D protein structure prediction.

ABSTRACT: We recently diagnosed a patient with pulmonary alveolar microlithiasis (PAM). Because loss-of-function mutations of the SLC34A2 gene are responsible for the development of PAM, we sought to sequence the SLC34A2 gene of the patient and his direct relatives, with a purpose to identify mutations that caused the PAM of the patient as well as the carriers of his family. We found a novel compound heterozygous mutation of the SLC34A2 gene in this patient, which were the mutations of c.1363T > C (p. Y455H) in exon 12 and c.910A > T (p. K304X) in exon 8. Computational prediction of three-dimensional (3D) structures of the mutants revealed that the Y455H mutation resulted in a formation of irregular coils in the trans-membrane domain and the K304X mutation resulted in protein truncation. Our study suggested that sequencing of the SLC34A2 gene together with a computational prediction of the 3D structures of the mutated proteins may be useful in PAM diagnosis and prognosis.

SUBMITTER: Wang H

PROVIDER: S-EPMC4287860 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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SLC34A2 gene compound heterozygous mutation identification in a patient with pulmonary alveolar microlithiasis and computational 3D protein structure prediction.

Wang Huiying H Yin Xinzhen X Wu Dingwen D Jiang Xinguo X

Meta gene 20140815

We recently diagnosed a patient with pulmonary alveolar microlithiasis (PAM). Because loss-of-function mutations of the SLC34A2 gene are responsible for the development of PAM, we sought to sequence the SLC34A2 gene of the patient and his direct relatives, with a purpose to identify mutations that caused the PAM of the patient as well as the carriers of his family. We found a novel compound heterozygous mutation of the SLC34A2 gene in this patient, which were the mutations of c.1363T > C (p. Y45 ...[more]

PMID: 25606438

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Project description:Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive lung disease caused by variants in the SLC34A2 gene encoding the sodium-dependent phosphate transport protein 2B, NaPi-2b. PAM is characterized by deposition of calcium phosphate crystals in the alveoli. Onset and clinical course vary considerably; some patients remain asymptomatic while others develop severe respiratory failure with a significant symptom burden and compromised survival. It is likely that PAM is under-reported due to lack of recognition, misdiagnosis, and mild clinical presentation. Most patients are genetically uncharacterized as the diagnostic confirmation of PAM has traditionally not included a genetic analysis. Genetic testing may in the future be the preferred tool for diagnostics instead of invasive methods. This systematic review aims to provide an overview of the growing knowledge of PAM genetics. Rare variants in SLC34A2 are found in almost all genetically tested patients. So far, 34 allelic variants have been identified in at least 68 patients. A majority of these are present in the homozygous state; however, a few are found in the compound heterozygous form. Most of the allelic variants involve only a single nucleotide. Half of the variants are either nonsense or frameshifts, resulting in premature termination of the protein or decay of the mRNA. There is currently no cure for PAM, and the only effective treatment is lung transplantation. Management is mainly symptomatic, but an improved understanding of the underlying pathophysiology will hopefully result in development of targeted treatment options. More standardized data on PAM patients, including a genetic diagnosis covering larger international populations, would support the design and implementation of clinical studies to the benefit of patients. Further genetic characterization and understanding of how the molecular changes influence disease phenotype will hopefully allow earlier diagnosis and treatment of the disease in the future.

Dataset Information

SLC34A2 gene compound heterozygous mutation identification in a patient with pulmonary alveolar microlithiasis and computational 3D protein structure prediction.

Publications

SLC34A2 gene compound heterozygous mutation identification in a patient with pulmonary alveolar microlithiasis and computational 3D protein structure prediction.

Similar Datasets

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