Other Diffuse Lung Diseases: Diffuse Cystic Lung Diseases (LAM, TSC, BHD), Sarcoidosis, Pulmonary Alveolar Proteinosis, and Pulmonary Alveolar Microlithiasis—What Are the Roles of Genetic Factors in the Pathogenesis of These Diseases?
Lymphangioleiomyomatosis (LAM) is a rare multisystem disorder that mostly affects women in their reproductive years and predominantly affects the lungs. LAM occurs in patients with tuberous sclerosis complex (TSC-LAM) and as a sporadic form in patients who do not have tuberous sclerosis (S-LAM). Patients with TSC-LAM have germline mutations either in TSC1 located on chromosome 9q34 or TSC2 located on chromosome 16p13.3, and the majority have a germline mutation in TCS2.
Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder that is characterized by the development of cutaneous fibrofolliculomas, renal tumors, and pulmonary cysts, causing spontaneous pneumothorax. BHD is caused by germline mutations in the folliculin (FLCN) gene on chromosome 17 (17p12q11.2), which encodes the protein FLCN.
Sarcoidosis is a systemic granulomatous disease that affects young and middle-aged adults. It frequently presents with bilateral hilar lymphadenopathy, pulmonary infiltration, and ocular and skin lesions. Granuloma formation is caused by T-cell activation by antigen presentation; therefore, the most prominent finding was a linkage to a section within human leukocyte antigens (HLA), a linkage to HLA-DRB1-alleles, and variants of these alleles are associated with the disease course and specific organ involvement.
Pulmonary alveolar proteinosis (PAP) is a rare disease in which surfactants mainly accumulate in the alveolar space due to the dysregulation of surfactant clearance by AMs. GM-CSF receptor gene mutations, surfactant-related genes SFTPB and SFTPC, gene mutations in ATP-binding cassette 3 (ABCA3), which is essential for the intracellular transport of surfactant, and NK2 homeobox 1 (NKX2-1), which is essential for the development of alveolar epithelial cells, have been reported in PAP patients.
Pulmonary alveolar microlithiasis (PAM) is an extremely rare disease and an autosomal recessive genetic disorder. Inactivating mutations are present in the solute carrier family 34 member 2 (SLC34A2) gene, which encodes the Ilb type sodium-dependent phosphoryl transport protein.
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