Two variants in the ubiquitously expressed NHLRC2 gene have been reported to cause a lethal fibrotic cerebropulmonary disease termed fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome in three Finnish children. Our objective was to determine the genetic basis of disease in a new patient with clinical features of FINCA syndrome using whole-exome sequencing (WES) and confirmation by Sanger sequencing. The patient has one known and one novel variant in NHLRC2 (c.442T>G, p.D148Y and c.428C>A, p.H143P, respectively). p.H143P is extremely rare and is not present in the gnomAD database of >140,000 allele sequences from healthy humans. Both variants affect the highly conserved N-terminal thioredoxin (Trx)-like domain of NHLRC2 and are predicted to be damaging. We conclude that a compound heterozygous combination of a known and a novel variant in NHLRC2 causes FINCA syndrome in a 2-year-old Ukrainian patient, underscoring the importance of NHLRC2 as a central regulator of fibrosis.

中文翻译：

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FINCA综合征患者的NHLRC2中新的复合杂合变异体。

据报道，在三个芬兰儿童中，普遍表达的NHLRC2基因中的两个变异体可导致致命的纤维化性脑肺疾病，称为纤维化，神经变性和脑血管瘤（FINCA）综合征。我们的目标是使用全外显子组测序（WES）并通过Sanger测序确认具有FINCA综合征临床特征的新患者的疾病遗传基础。该患者在NHLRC2中有一个已知的和一个新的变体（分别为c.442T> G，p.D148Y和c.428C> A，p.H143P）。p.H143P非常罕见，并且在来自健康人类的> 140,000个等位基因序列的gnomAD数据库中不存在。这两个变体均会影响NHLRC2的高度保守的N端硫氧还蛋白（Trx）样结构域，并预计会造成破坏。