In 2014, a child with broad combined immunodeficiency (CID) who was homozygous for a private BCL10 allele was reported to have complete inherited human BCL10 deficiency. In the present study, we report a new BCL10 mutation in another child with CID who was homozygous for a BCL10 variant (R88X), previously reported as a rare allele in heterozygosis (minor allele frequency, 0.000003986). The mutant allele was a loss-of-expression and loss-of-function allele. As with the previously reported patient, this patient had complete BCL10 deficiency. The clinical phenotype shared features, such as respiratory infections, but differed from that of the previous patient that he did not develop significant gastroenteritis episodes or chronic colitis. Cellular and immunological phenotypes were similar to those of the previous patient. TLR4, TLR2/6, and Dectin-1 responses were found to depend on BCL10 in fibroblasts, and final maturation of T cell and B cell maturation into memory cells was affected. Autosomal-recessive BCL10 deficiency should therefore be considered in children with CID.

中文翻译：

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罕见等位基因纯合性导致的人类BCL10缺乏症。

2014年，据报道一名儿童的广泛综合免疫缺陷症（CID）与私人BCL10等位基因纯合，具有完全遗传的人类BCL10缺陷。在本研究中，我们报道了另一位CID儿童的新BCL10突变，该儿童对BCL10变体（R88X）是纯合的，以前被报道为杂合症中的罕见等位基因（次要等位基因频率为0.000003986）。突变等位基因是表达缺失和功能丧失等位基因。与先前报道的患者一样，该患者患有完全的BCL10缺乏症。临床表型具有呼吸道感染等特征，但与之前的患者不同，他没有出现明显的胃肠炎发作或慢性结肠炎。细胞和免疫表型与先前患者相似。TLR4，TLR2 / 6，发现Dectin-1和Dectin-1反应依赖于成纤维细胞中的BCL10，并且影响了T细胞的最终成熟和B细胞成熟到记忆细胞中。因此，对于CID儿童，应考虑常染色体隐性BCL10缺乏症。