PHARC syndrome is a rare neurodegenerative disorder caused by mutations in the ABHD12 gene. It is a genetically heterogeneous and clinically variable disease, which is characterized by demyelinating polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early‐onset cataract and can easily be misdiagnosed as other neurologic disorders with a similar clinical picture, such as Charcot‐Marie‐Tooth disease and Refsum disease. We describe the genotype‐phenotype correlation of two siblings with a novel genotype underlying PHARC syndrome. The genotype was identified using next‐generation sequencing. We examined both patients by means of thorough history taking and clinical examination, nerve conduction studies (NCS), brain imaging, and optical coherence tomography to establish a genotype‐phenotype correlation. We identified a novel homozygous point mutation (c.784C > T, p.Arg262*) in the ABHD12 gene. This mutation was detected in both siblings, who had bilateral hearing loss and cataracts, signs of cerebellar ataxia, and neuropathy with a primarily demyelinating pattern in NCS. In one case, retinitis pigmentosa was also evident. As PHARC syndrome is a rare autosomal recessive disorder, our findings highlight the importance of an interdisciplinary diagnostic workup with clinical and molecular genetic testing to avoid a misdiagnosis as Charcot‐Marie‐Tooth disease or Refsum disease.

中文翻译：

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潜在的PHARC综合征的新型ABHD12突变中的基因型与表型相关。

PHARC综合征是由ABHD12突变引起的罕见神经退行性疾病基因。它是一种遗传上异质且临床上可变的疾病，其特征是脱髓鞘性多发性神经病，听力损失，小脑性共济失调，色素性视网膜炎和早发性白内障，并且很容易被误诊为其他具有类似临床表现的神经系统疾病，例如Charcot-玛丽牙病和Refsum病。我们描述了具有潜在PHARC综合征新基因型的两个兄弟姐妹的基因型与表型的相关性。使用下一代测序鉴定了基因型。我们通过全面的病史和临​​床检查，神经传导研究（NCS），脑成像以及光学相干断层扫描检查了这两名患者，以建立基因型与表型的相关性。我们确定了一个新的纯合子点突变（c.784C> T，p.Arg262 *）在ABHD12基因。在两个患有双侧听力损失和白内障，小脑性共济失调和神经病的兄弟姐妹中都检测到了这种突变，NCS的病史主要是脱髓鞘。在一种情况下，色素性视网膜炎也很明显。由于PHARC综合征是一种罕见的常染色体隐性遗传疾病，因此我们的发现凸显了进行跨学科诊断检查以及临床和分子遗传学检测对避免误诊为Charcot-Marie-Tooth病或Refsum病的重要性。