A newly identified novel variant in the CSF2RA gene in a child with pulmonary alveolar proteinosis: a case report

Abstract

BackgroundThe congenital form of pulmonary alveolar proteinosis due to colony stimulating factor 2 receptor alpha gene mutations is a rare disease with only a few cases reported worldwide. In this study we report a new case of pulmonary alveolar proteinosis with a novel variant in colony stimulating factor 2 receptor alpha gene.Case presentationA 5-year-old Saudi boy presented with a history of progressive dyspnea over 6 months; he was diagnosed as having pulmonary alveolar proteinosis. A molecular study revealed a novel variation in colony stimulating factor 2 receptor alpha gene. His clinical condition showed significant improvement after whole lung lavage.ConclusionsThis case has the typical presentation of congenital pulmonary alveolar proteinosis due to colony stimulating factor 2 receptor alpha defect with a novel variant in this gene likely to be pathogenic.

Methionyl-tRNA synthetase novel mutation causes pulmonary alveolar proteinosis

“…In the Kingdom of Saudi Arabia, there have been reports of PAP due to surfactant clearance and surfactant dysfunction disorder 9,10. Nevertheless, this is the first report of PAP due to MARS mutation in the Arabian Gulf region…”

Alveolar proteinosis of genetic origins

“…To date, 23 patients with CSF2RA mutations [19][20][21][22][23][24] and two patients with CSF2RB mutations [25,26] have been reported in the literature. 19 CSF2RA cases were reviewed in 2014 and four more patients were reported in 2017.…”

“…She was the sister of one patient diagnosed at the age of 6 years, and the diagnosis was suggested when she developed a cough [19]. Five individuals, aged <3, 3, 5, 7 and 8 years, were asymptomatic and genetically tested during the familial screening of their affected sibling [20,23,24]. One of them underwent a chest CT scan and bronchoalveolar lavage that confirmed the diagnosis of PAP, one only underwent a chest CT scan and the other three had no investigation other than molecular biology.…”

“…In the two patients reported by CHIU et al [23] (one boy with PAP and his asymptomatic brother) diagnosis was made by whole-genome sequencing of all family members. In the patient reported by AL-HAIDARY et al [24], diagnosis was made by next-generation sequencing of a panel that contains the genes involved in surfactant disorders. His family members were then screened for the mutation that was identified by Sanger sequencing and his sister, albeit asymptomatic, was homozygous for the same mutation.…”

“…# : information missing for five patients. Data from[19][20][21][22][23][24]. https://doi.org/10.1183/16000617.0187-2019…”