Mutations in the <i>SLC34A2</i> Gene Are Associated with Pulmonary Alveolar Microlithiasis

Huqun,; Izumi, Satoshi; Miyazawa, Hitoshi; Ishii, Kuniaki; Uchiyama, Bine; Ishida, Tadashi; Tanaka, Sawako; Tazawa, Ryushi; Fukuyama, Shunichiro; Tanaka, Tomoaki; Nagai, Yoshinori; Yokote, Akemi; Takahashi, Hiroki; Fukushima, Toshihiko; Kobayashi, Kunihiko; Chiba, Hirofumi; Nagata, Michio; Sakamoto, Susumu; Nakata, Kohei; Takebayashi, Yuji; Shimizu, Yoshihiko; Kaneko, Koichi; Shimizu, Mayuko; Kanazawa, Minoru; Abe, Shosaku; Inoue, Yoshikazu; Takenoshita, Seiichi; Yoshimura, Kazuya; Kudo, Kohsuke; Tachibana, T; Nukiwa, Toshihiro; Hagiwara, Koichi

doi:10.1164/rccm.200609-1274oc

Cited by 172 publications

(133 citation statements)

References 15 publications

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“…Hence, the significance of the constitutive 'non-ROH' segmental UPD traits found in infant ALL patients and whether they could have a role in the leukemogenic progress still remain to be determined. Indeed, extended 'runs of homozygosity' in the Table 3 Recurrent UPD human genome have been found not only in patients [21][22][23] but also in healthy individuals; [23][24][25] therefore, UPDs could represent previously undetected new ROH, which are not involved in the pathogenesis of the disease. Conversely, it cannot be excluded that genomic background, characterized by constitutional stretches of homozygosity, might offer a permissive environment for the development of the disease, favoring the occurrence of the MLL rearrangement itself, although further work is required to explore this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…ROHs among unrelated patients lead to the identification of new genes or candidate loci responsible for the genetic basis of the disease. [23][24][25] In this study, we explored the genomic profile of infant ALL by SNP array to detect MLL-cooperating aberrations, hidden to conventional techniques. To further limit heterogeneity, we focused on patients carrying the t(4;11) translocation, which is the most frequent genetic abnormality in infant ALL.…”

Section: Introductionmentioning

confidence: 99%

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DNA copy-number abnormalities do not occur in infant ALL with t(4;11)/MLL-AF4

et al. 2009

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The pathogenesis of infant acute lymphoblastic leukemia (ALL) is still not well defined. Short latency to leukemia and very high concordance rate for ALL in Mixed-Lineage Leukemia (MLL)-positive infant twins suggest that the MLL rearrangement itself could be sufficient for overt leukemia. Attempts to generate a suitable mouse model for MLL-AF4-positive ALL did not thoroughly resolve the issue of whether cooperating mutations are required to reduce latency and to generate overt leukemia in vivo. In this study, we applied single-nucleotide polymorphism array technology to perform genomic profiling of 28 infant ALL cases carrying t(4;11) to detect MLL-cooperating aberrations hidden to conventional techniques and to gain new insights into infant ALL pathogenesis. In contrast to pediatric, adolescent and adult ALL cases, the MLL rearrangement in infant ALL is associated with an exceptionally low frequency of copy-number abnormalities, thus confirming the unique nature of this disease. By contrast, additional genetic aberrations are acquired at disease relapse. Small-segmental uniparental disomy traits were frequently detected, mostly constitutional, and widely distributed throughout the genome. It can be argued that the MLL rearrangement as a first hit, rather than inducing the acquisition of additional genetic lesions, has a major role to drive and hasten the onset of leukemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA copy-number abnormalities do not occur in infant ALL with t(4;11)/MLL-AF4

et al. 2009

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“…Individuals with homozygous Npt2b loss-of-function mutations develop pulmonary alveolar microlithiasis (76,77), an unusual disorder characterized by the development of respiratory failure accompanied by alveolar calcifications in middle age. Some patients exhibit calcifications in a number of other organs in which Npt2b mRNA has been identified, including kidneys, pleura, seminal vesicles, urethra, and gall bladder.…”

Section: Npt2bmentioning

confidence: 99%

Clinical Consequences of Mutations in Sodium Phosphate Cotransporters

Lederer

Miyamoto

2012

Clinical Journal of the American Society of Nephrology

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SummaryThree families of sodium phosphate cotransporters have been described. Their specific roles in human health and disease have not been defined. Review of the literature reveals that the type II sodium phosphate cotransporters play a significant role in transepithelial transport in a number of tissues including kidney, intestine, salivary gland, mammary gland, and lung. The type I transporters seem to play a major role in renal urate handling and mutations in these proteins have been implicated in susceptibility to gout. The ubiquitously expressed type III transporters play a lesser role in phosphate homeostasis but contribute to cellular phosphate uptake, mineralization, and inflammation. The recognition of species differences in the expression, regulation, and function of these transport proteins suggests an urgent need to find ways to study them in humans.

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“…It is inherited with an autosomal recessive pattern. 10,11 SLC34A2 is mainly expressed in the lung and mammary glands, and to a lesser extent in the intestine, kidneys, and prostate. This is the only phosphate transporter that is highly expressed in the lung, specifically in type II alveolar cells.…”

Section: Discussionmentioning

confidence: 99%

Bilateral Micronodular Pulmonary Infiltrate: Is It Important to Make a Histological Diagnosis?

Khan

Gilmartin

2012

Respir Care

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Pulmonary alveolar microlithiasis is a rare disease characterized by the deposition of calcium phosphate within the alveoli. We report the case of a 20-year-old man with a 6-week history of cough and shortness of breath on exertion. The chest radiograph demonstrated a bilateral symmetrical micronodular pattern. High-resolution computed tomography revealed bilateral diffuse fine nodular shadowing involving the mid zones, with sparing of the apices. The patient underwent a transbronchial lung biopsy, which confirmed the diagnosis of pulmonary alveolar microlithiasis.

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Mutations in the SLC34A2 Gene Are Associated with Pulmonary Alveolar Microlithiasis

Abstract: Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis.

Cited by 172 publications

References 15 publications

DNA copy-number abnormalities do not occur in infant ALL with t(4;11)/MLL-AF4

DNA copy-number abnormalities do not occur in infant ALL with t(4;11)/MLL-AF4

Clinical Consequences of Mutations in Sodium Phosphate Cotransporters

Bilateral Micronodular Pulmonary Infiltrate: Is It Important to Make a Histological Diagnosis?

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