Purpose

Biallelic variants in TBC1D24, which encodes a protein that regulates vesicular transport, are frequently identified in patients with DOORS (deafness, onychodystrophy, osteodystrophy, intellectual disability [previously referred to as mental retardation], and seizures) syndrome. The aim of the study was to identify a genetic cause in families with DOORS syndrome and without a TBC1D24 variant.

Methods

Exome or Sanger sequencing was performed in individuals with a clinical diagnosis of DOORS syndrome without TBC1D24 variants.

Results

We identified the same truncating variant in ATP6V1B2 (NM_001693.4:c.1516C>T; p.Arg506*) in nine individuals from eight unrelated families with DOORS syndrome. This variant was already reported in individuals with dominant deafness onychodystrophy (DDOD) syndrome. Deafness was present in all individuals, along with onychodystrophy and abnormal fingers and/or toes. All families but one had developmental delay or intellectual disability and five individuals had epilepsy. We also describe two additional families with DDOD syndrome in whom the same variant was found.

Conclusion

We expand the phenotype associated with ATP6V1B2 and propose another causal gene for DOORS syndrome. This finding suggests that DDOD and DOORS syndromes might lie on a spectrum of clinically and molecularly related conditions.

中文翻译：

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DOORS 综合征和复发性截断 ATP6V1B2 变体。

目的

TBC1D24 中的双等位基因变体编码一种调节水泡运输的蛋白质，经常在 DOORS（耳聋、甲营养不良、骨营养不良、智力障碍 [以前称为智力迟钝] 和癫痫发作）综合征患者中发现。该研究的目的是确定患有 DOORS 综合征且没有TBC1D24变异的家庭的遗传原因。

方法

在临床诊断为 DOORS 综合征且无​​ TBC1D24变异体的个体中进行外显子组或 Sanger 测序。

结果

我们在来自 8 个具有 DOORS 综合征的无关家庭的 9 个个体中发现了相同的 ATP6V1B2 截断变体( NM_001693.4:c.1516C>T; p.Arg506*)。这种变异已经在患有显性耳聋甲营养不良（DDOD）综合征的个体中报道。所有个体都存在耳聋，以及甲营养不良和异常的手指和/或脚趾。除一个家庭外，所有家庭都有发育迟缓或智力障碍，五个人患有癫痫症。我们还描述了另外两个患有 DDOD 综合征的家族，其中发现了相同的变异。

结论

我们扩展了与 ATP6V1B2 相关的表型，并提出了 DOORS 综合征的另一个因果基因。这一发现表明 DDOD 和 DOORS 综合征可能存在于一系列临床和分子相关疾病。