Primary familial brain calcification (PFBC) is a well-known genetic condition that has recently had a surge of autosomal recessive cases. We recently reported a case of autosomal recessive PFBC on a 54-year-old Brazilian patient with a novel homozygous variant on MYORG. Interestingly, that patient also had a series of uncommon signs and symptoms, including Hashimoto’s thyroiditis, polyneuropathy, optic nerve head drusen (ONHD), and persistent anemia. We chose to perform whole exome sequencing (WES) to possibly detect other unknown genetic conditions that could explain the extra-neurological findings reported. WES confirmed the presence of the MYORG variant previously reported by us, and determined the presence of a heterozygous nonsense variant on HBB (c.118C > T, p.Q40*), defining a diagnosis of beta-thalassemia. Based on literature review, the new WES finding explains the persistent anemia and polyneuropathy shown by the patient, while still leaving the ONHD and autoimmune thyroiditis without a clear genetic link. This way, we propose that these novel clinical findings could be linked to MYORG, but still encourage further studies to evaluate this possibility.

中文翻译：

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巴西受试者大脑钙化与新型表型有关的重叠疾病。

原发性家族性脑钙化（PFBC）是一种众所周知的遗传病，最近已出现常染色体隐性遗传病例。我们最近报道了一名54岁的巴西患者常染色体隐性隐性PFBC病例，该患者在MYORG上具有新型纯合变异。有趣的是，该患者还出现了一系列不常见的体征和症状，包括桥本氏甲状腺炎，多发性神经病，视神经头玻璃疣（ONHD）和持续性贫血。我们选择执行全外显子组测序（WES），以检测可能解释所报道的神经外发现的其他未知遗传状况。WES确认了我们先前报告的MYORG变体的存在，并确定了HBB上杂合的无意义变体的存在（c.118C> T，p.Q40 *），定义为β地中海贫血的诊断。根据文献综述，新的WES发现可以解释患者表现出的持续性贫血和多发性神经病，同时仍然使ONHD和自身免疫性甲状腺炎没有明确的遗传联系。这样，我们建议将这些新颖的临床发现与MYORG相关联，但仍鼓励进行进一步的研究以评估这种可能性。