Background Pulmonary alveolar microlithiasis (PAM) is caused by genetic variants in the SLC34A2 gene, which encodes the sodium-dependent phosphate transport protein 2B (NaPi-2b). PAM is characterised by deposition of calcium phosphate concretions (microliths) in the alveoli leading to pulmonary dysfunction. The variant spectrum of SLC34A2 has not been well investigated and it is not yet known whether a genotype–phenotype correlation exists. Methods We collected DNA from 14 patients with PAM and four relatives, and analysed the coding regions of SLC34A2 by direct DNA sequencing. To determine the phenotype characteristics, clinical data were collected and a severity score was created for each variant, based on type and localisation within the protein. Results We identified eight novel allelic variants of SLC34A2 in 14 patients with PAM. Four of these were nonsense variants, three were missense and one was a splice site variant. One patient was heterozygous for two different variants and all other patients were homozygous. Four patients were asymptomatic and 10 patients were symptomatic. The severity of the disease was associated with the variant severity. Conclusions Our findings support a significant role for SLC34A2 in PAM and expand the variant spectrum of the disease. Thus, SLC34A2 variants were detected in all patients and eight novel allelic variants were discovered. An association between disease severity and the severity of the variants was found; however, this needs to be investigated in larger patient populations. Eight novel variants in the SLC34A2 gene have been identified in 14 patients with pulmonary alveolar microlithiasis (PAM), which emphasises the importance of the gene in the disease. Furthermore, a genotype–phenotype correlation in PAM may exist. http://bit.ly/3307M1p

中文翻译：

---

肺泡微石症中 SLC34A2 基因的八种新变体

背景 肺泡微石症 (PAM) 是由 SLC34A2 基因的遗传变异引起的，该基因编码钠依赖性磷酸盐转运蛋白 2B (NaPi-2b)。PAM 的特点是在肺泡中沉积磷酸钙结石（微石），导致肺功能障碍。SLC34A2 的变异谱尚未得到很好的研究，尚不清楚是否存在基因型-表型相关性。方法收集14例PAM患者及其4名亲属的DNA，通过直接DNA测序分析SLC34A2的编码区。为了确定表型特征，收集临床数据并根据蛋白质内的类型和定位为每个变体创建严重程度评分。结果 我们在 14 名 PAM 患者中发现了 8 个新的 SLC34A2 等位基因变体。其中四个是无义变体，三个是错义变体，一个是剪接位点变体。一名患者是两种不同变体的杂合子，所有其他患者都是纯合子。4名患者无症状，10名患者有症状。疾病的严重程度与变异的严重程度有关。结论 我们的研究结果支持 SLC34A2 在 PAM 中的重要作用，并扩大了该疾病的变异谱。因此，在所有患者中均检测到 SLC34A2 变体，并发现了八种新的等位基因变体。发现疾病严重程度与变异严重程度之间存在关联；然而，这需要在更大的患者群体中进行调查。已在 14 名肺泡微石症 (PAM) 患者中鉴定出 SLC34A2 基因的八种新变体，这强调了基因在疾病中的重要性。此外，PAM 中可能存在基因型-表型相关性。http://bit.ly/3307M1p