Federal University of Vale do São Francisco, Petrolina, Pernambuco, Brazil.
School of Medicine of Ribeirão Preto, São Paulo State University, São Paulo, Brazil.
J Hum Genet. 2020 Aug;65(8):711-713. doi: 10.1038/s10038-020-0749-3. Epub 2020 Apr 9.
Amyloidosis, caused by a mutation in the transthyretin (TTR) gene, is the most common hereditary type disease. More than 120 mutations have been described, with extensive phenotypic heterogeneity. Val30Met (p.Val50Met) is the most frequent mutation, and patients exhibit polyneuropathy, possibly including cardiac, renal, gastrointestinal, and/or ocular involvement. Val122Ile (p.Val142Ile) is the mutation associated with cardiomyopathy, and few cases have been reported in Brazil. Most individuals are heterozygous for one pathogenic mutation. Herein, we report a compound heterozygote with two pathogenic mutations (Val30Met/ Val122Ile), and a family history of a deceased brother with amyloidosis, who also carried the same TTR gene mutations. The patient presented with neuropathic, cardiac, and renal impairment and a faster disease progression. Cases of the double mutation have been linked to changes in disease presentation. The concomitance of two pathogenic mutations may have contributed to more exuberant manifestations and faster disease progression.
淀粉样变性由转甲状腺素蛋白（TTR）基因突变引起，是最常见的遗传性疾病类型。已经描述了超过 120 种突变，具有广泛的表型异质性。Val30Met（p.Val50Met）是最常见的突变，患者表现为多发性神经病，可能包括心脏、肾脏、胃肠道和/或眼部受累。Val122Ile（p.Val142Ile）与心肌病相关，在巴西报道的病例较少。大多数个体为一种致病性突变的杂合子。在此，我们报告了一例复合杂合子，携带两种致病性突变（Val30Met/Val122Ile），且有家族史，其已故的哥哥也患有淀粉样变性，同样携带相同的 TTR 基因突变。该患者表现为周围神经病、心脏和肾脏损害，且疾病进展较快。双重突变的病例与疾病表现的变化有关。两种致病性突变的共存可能导致更明显的表现和更快的疾病进展。
