Pathogenic variants in the MBTPS1 gene encoding the Site 1 protease have been described so far only in one growth retarded patients with skeletal deformities, large ears, a triangular face reminiscent to Silver–Russell syndrome (SRS), and elevated blood lysosomal enzymes. We now report on the identification of a second adult patient homozygous for one of the two published pathogenic MBTPS1 variants (p.Asp365Gly) by Whole Exome Sequencing (WES), and a comparable phenotype. With this case, the association of pathogenic variants in MBTPS1 with a recognizable disorder could be confirmed, and the autosomal recessive inheritance is further established. As the variant was identified after a long diagnostic odyssey of the family, this example illustrates the need to apply WES in the diagnostic workup in case of growth retardation as early as possible. By compiling the clinical data of this new patient with those of the already reported patient, a better prognosis for future patients with MBTPS1 variants can be issued, and clinical management can be adjusted.

中文翻译：

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具有常染色体隐性MBTPS1相关表型和银-罗素综合征临床特征的患者。

迄今为止，仅在一位生长发育迟缓的患者中描述了编码Site 1蛋白酶的MBTPS1基因的致病变异，这些患者患有骨骼畸形，大耳朵，让人联想到Silver-Russell综合征（SRS）的三角形脸和血液溶酶体酶升高。我们现在报告通过全外显子组测序（WES）和两个可比较的表型鉴定两个已发布的病原性MBTPS1变体（p.Asp365Gly）之一的第二个成年患者纯合子。在这种情况下，MBTPS1中的致病变异可以确认患有可识别的疾病，并进一步建立常染色体隐性遗传。由于该变体是在该家庭经历了漫长的诊断旅程之后才被鉴定出来的，因此本示例说明了在生长迟缓的情况下尽早将WES用于诊断检查的必要性。通过将这个新患者的临床数据与已经报道的患者的临床数据进行汇总，可以为未来患有MBTPS1变异的患者提供更好的预后，并可以调整临床管理。