DOORS [deafness, onychodystrophy, osteodystrophy, intellectual disability (mental retardation), and seizures] syndrome can be caused by mutations in the TBC1D24 and ATP6V1B2 genes, both of which are involved in endolysosomal function. Because of its extreme rarity, to date, no detailed neuropathological assessment has been performed to establish clinicopathological relationships and, thereby, understand better the neurobiology of this disease in aged cases. Accordingly, the aim of the current study was to highlight the clinicopathological characteristics of a novel case with a presumable de novo mutation in the ATP6V1B2 gene from a neuropathological point of view. This Caucasian male patient, who died at the age of 72 years, presented all the typical cardinal signs of DOORS syndrome. In addition, behavioral alterations, pyramidal signs, and Parkinsonism were observed. The p.R506X pathogenic mutation identified in the ATP6V1B2 gene was responsible for the clinical phenotype. The detailed neuropathological assessment revealed a limbic-predominant tauopathy in the forms of argyrophilic grain disease, primary age-related tauopathy, and age-related tau-astrogliopathy. In summary, we present the first detailed clinicopathological report of a patient with DOORS syndrome harboring a pathogenic mutation in the ATP6V1B2 gene. The demonstrated tauopathy may be considered as a consequence of lysosomal and/or mitochondrial dysfunction, similar to that found in Niemann-Pick type C disease, which is another lysosomal disorder characterized by premature neurodegenerative disorder.

中文翻译：

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DOORS综合征老年病例中ATP6V1B2基因p.Arg506X突变的临床病理关系。

DOORS [聋，甲状肌营养不良，骨营养不良，智力障碍（智力低下）和癫痫发作]综合征可能是由于TBC1D24和ATP6V1B2基因的突变引起的，这两种基因均与溶酶体功能有关。迄今为止，由于其极为罕见，因此尚未进行详细的神经病理学评估以建立临床病理关系，从而更好地理解该疾病在老年患者中的神经生物学。因此，本研究的目的是从神经病理学的角度突出一例在ATP6V1B2基因中具有从头突变的新病例的临床病理特征。这位白人男性患者享年72岁，死亡，表现出DOORS综合征的所有典型基本体征。此外，行为改变，金字塔形标志，和帕金森症。ATP6V1B2基因中鉴定出的p.R506X致病突变是临床表型的原因。详细的神经病理学评估显示，以嗜银粒病，原发性年龄相关性tauopathy和年龄相关性tau-星形胶质细胞增生的形式存在边缘为主的tauopathy。总而言之，我们提出了第一例详细的DOORS综合征患者的临床病理报告，该患者在ATP6V1B2基因中存在致病性突变。所证明的tauopathy可能被认为是溶酶体和/或线粒体功能障碍的结果，类似于Niemann-Pick C型疾病中发现的那种，后者是另一种以早发性神经退行性疾病为特征的溶酶体疾病。ATP6V1B2基因中鉴定出的R506X致病突变是临床表型的原因。详细的神经病理学评估显示，以嗜银粒病，原发性年龄相关性tauopathy和年龄相关性tau-星形胶质细胞增生的形式存在边缘为主的tauopathy。总而言之，我们提出了第一例详细的DOORS综合征患者的临床病理报告，该患者在ATP6V1B2基因中存在致病性突变。所证明的tauopathy可被认为是溶酶体和/或线粒体功能障碍的结果，类似于Niemann-Pick C型疾病中发现的那种，后者是另一种以过早的神经退行性疾病为特征的溶酶体疾病。ATP6V1B2基因中鉴定出的R506X致病突变是临床表型的原因。详细的神经病理学评估显示，以嗜银粒病，原发性年龄相关性tauopathy和年龄相关性tau-星形胶质细胞增生的形式存在边缘为主的tauopathy。总而言之，我们提出了患有DOORS综合征的患者的第一份详细的临床病理报告，该患者在ATP6V1B2基因中具有致病性突变。所证明的tauopathy可被认为是溶酶体和/或线粒体功能障碍的结果，类似于Niemann-Pick C型疾病中发现的那种，后者是另一种以过早的神经退行性疾病为特征的溶酶体疾病。原发性与年龄有关的tauopathy和与年龄有关的tau-星形神经胶质病。总而言之，我们提出了第一例详细的DOORS综合征患者的临床病理报告，该患者在ATP6V1B2基因中存在致病性突变。所证明的tauopathy可能被认为是溶酶体和/或线粒体功能障碍的结果，类似于Niemann-Pick C型疾病中发现的那种，后者是另一种以早发性神经退行性疾病为特征的溶酶体疾病。原发性与年龄有关的tauopathy和与年龄有关的tau-星形神经胶质病。总而言之，我们提出了第一例详细的DOORS综合征患者的临床病理报告，该患者在ATP6V1B2基因中存在致病性突变。所证明的tauopathy可被认为是溶酶体和/或线粒体功能障碍的结果，类似于Niemann-Pick C型疾病中发现的那种，后者是另一种以过早的神经退行性疾病为特征的溶酶体疾病。