Badura-Stronka Magdalena, Hirschfeld Adam Sebastian, Globa Evgenia, Winczewska-Wiktor Anna, Potulska-Chromik Anna, Kostera-Pruszczyk Anna, Wicher Dorota, Krawczyński Maciej Robert
Chair and Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
Centers for Medical Genetics GENESIS, Poznan, Poland.
J Appl Genet. 2025 May;66(2):363-373. doi: 10.1007/s13353-024-00894-9. Epub 2024 Aug 17.
We report three patients with the novel variant c.100 + 1G > A of the TBCE gene and describe the presented clinical phenotype in detail. We also systematically reviewed the literature for clinical similarities and dissimilarities among all known patients with pathogenic TBCE variants. The clinical phenotype observed in patients with pathogenic TBCE variants is broader than previously described. Homozygous carriers of the c.100 + 1G > A variant exhibit a markedly milder clinical course, with no deviations in the calcium-phosphate metabolism and central nervous system pathology in MRI studies. Additionally, two patients manifest highly specific symptoms such as a rigid spine, eosinophilia, neutropenia, and nocturnal hypoxemia. Furthermore, cryptorchidism was observed in male patients. The identification of the pathogenic c.100 + 1G > A variant has thus far been limited to patients of Central-Eastern European descent, suggesting a potential founder mutation in this population.
我们报告了三名携带TBCE基因新型变异c.100 + 1G > A的患者,并详细描述了所呈现的临床表型。我们还系统回顾了文献,以了解所有已知携带致病性TBCE变异患者之间的临床异同。携带致病性TBCE变异患者所观察到的临床表型比先前描述的更为广泛。c.100 + 1G > A变异的纯合携带者表现出明显较轻的临床病程,在MRI研究中钙磷代谢和中枢神经系统病理学无异常。此外,两名患者表现出高度特异性症状,如脊柱僵硬、嗜酸性粒细胞增多、中性粒细胞减少和夜间低氧血症。此外,在男性患者中观察到隐睾症。迄今为止,致病性c.100 + 1G > A变异的鉴定仅限于中东欧血统的患者,提示该人群中可能存在奠基者突变。