Differences in genetic characteristics between Chinese and non-Chinese patients with pulmonary alveolar microlithiasis-case series and a systematic review.

BACKGROUND

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disorder caused by variants, characterized by diffuse alveolar calcium phosphate deposits. While the mutation spectrum has been well-documented, the distinct variant landscape in Chinese patients remains unclear.

OBJECTIVES

This study aims to report three newly identified PAM cases and describe the mutation spectrum of Chinese PAM patients through a systematic review.

DESIGN

We documented the diagnosis and treatment processes and genetic variations of three PAM cases for reporting. Furthermore, we searched academic websites for published PAM cases with variants and extracted clinical and genetic data for analysis.

METHODS

We employed whole-exome sequencing to identify genetic mutations of these three patients. We systematically searched PubMed, Web of Science, China National Knowledge Infrastructure, and Cochrane Library for published PAM cases with mutations. Clinical and genetic data were extracted into an Excel database and analyzed using SPSS 23.0 software (IBM, Armonk, NY, USA).

RESULTS

Among the three cases we reported, two homozygous mutations in -c.910A>T (p.Lys304*) in exon 8 and c.575C>A (p.Thr192Lys) in exon 6 were identified. Analysis of 27 Chinese and 49 non-Chinese PAM patients revealed similar clinical manifestations, but a strikingly distinct genetic spectrum. Compound heterozygous mutations predominated in Chinese patients, while only two cases of compound heterozygous mutations were found in non-Chinese patients. Deletion/insertion mutations are the most common in non-Chinese patients (19/47, 40.4%), whereas nonsense mutations are the most frequent in Chinese patients (12/20, 60%). Further analysis of the reported mutation sites in Chinese PAM patients showed hotspot regions in exons 5, 6, and 8, with c.910A>T in exon 8 being a unique gene screening target in Chinese patients.

CONCLUSION

This study delineates a distinct spectrum of mutations in Chinese PAM patients, highlighting the importance of ethnicity-specific genetic screening in PAM diagnosis.