Despite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22–2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08–2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29–2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis.

Sarcoidosis is a multi-organ granulomatous disease of unknown etiology. Neurological involvement in sarcoidosis is uncommon but cranial mononeuropathies, especially involving the VII and VIII cranial nerves, are highly suggestive of neurosarcoidosis. We report the case of a 54-year-old woman who presented with fever, night sweats, weight loss, polyarthralgia, and bilateral hearing loss. Mediastinal and hilar lymphadenopathies with hypercaptation on positive emission tomography (PET) scans were present. Low-dose steroids were ineffective. She then developed bilateral anterior uveitis and right-sided peripheral facial palsy. Head magnetic resonance imaging (MRI) showed inflammatory involvement of the right cochlea, geniculate ganglion, and bilateral vestibulocochlear bundle. Cerebrospinal fluid analysis was compatible with aseptic meningitis. Excisional biopsy of mediastinal lymph nodes confirmed the presence of noncaseating granulomas. The diagnosis of systemic sarcoidosis with serious neurological involvement was made and treatment with high-dose steroids led to significant clinical improvement. Sarcoidosis remains a diagnosis of exclusion based on supportive clinical, radiological, and histological findings. This case highlights the challenge it was to diagnose this disorder. Neurologic involvement in sarcoidosis is relatively uncommon and has an unpredictable clinical course and prognosis.

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