PDF(Pubmed)
Abstract：
The study aims to report a rare case of a novel homozygous variant in the LRBA gene, originating from uniparental disomy of paternal origin. This case contributes new clinical data to the LRBA gene variant database.
The study details the case of a 2-year-old child diagnosed in May 2023 at our center with a homozygous LRBA gene variant. Detailed clinical data of the patient were collected, including whole-exome sequencing of peripheral blood mononuclear cells, with parental genetic verification.
The child presented with recurrent respiratory infections and chronic neutropenia, progressing to pancytopenia. Imaging showed splenomegaly and enlarged lymph nodes in the axillary and abdominal regions. Peripheral blood lymphocyte count revealed reduced B cells and NK cells. Elevated cytokine levels of IFN-α and IFN-r were observed. Whole-exome sequencing revealed a nonsense homozygous variant in the LRBA gene, specifically c.2584C>T (p.Gln862Ter). The father exhibited a heterozygous variant at this locus, while no variant was found in the mother. Sample analysis indicated characteristics of uniparental disomy. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant is preliminarily classified as \"Likely pathogenic\". Currently, there are no reports in academic literature regarding this specific variant site.
LRBA gene variants can lead to a rare inborn error of immunity disease. The c.2584C>T (p.Gln862Ter) variant in exon 22 of the LRBA gene is a newly identified pathogenic variant, and the homozygous variant caused by uniparental disomy is exceedingly rare. This case represents the second global report of an LRBA gene function loss due to uniparental disomy abnormalities.
The study details the case of a 2-year-old child diagnosed in May 2023 at our center with a homozygous LRBA gene variant. Detailed clinical data of the patient were collected, including whole-exome sequencing of peripheral blood mononuclear cells, with parental genetic verification.
The child presented with recurrent respiratory infections and chronic neutropenia, progressing to pancytopenia. Imaging showed splenomegaly and enlarged lymph nodes in the axillary and abdominal regions. Peripheral blood lymphocyte count revealed reduced B cells and NK cells. Elevated cytokine levels of IFN-α and IFN-r were observed. Whole-exome sequencing revealed a nonsense homozygous variant in the LRBA gene, specifically c.2584C>T (p.Gln862Ter). The father exhibited a heterozygous variant at this locus, while no variant was found in the mother. Sample analysis indicated characteristics of uniparental disomy. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant is preliminarily classified as \"Likely pathogenic\". Currently, there are no reports in academic literature regarding this specific variant site.
LRBA gene variants can lead to a rare inborn error of immunity disease. The c.2584C>T (p.Gln862Ter) variant in exon 22 of the LRBA gene is a newly identified pathogenic variant, and the homozygous variant caused by uniparental disomy is exceedingly rare. This case represents the second global report of an LRBA gene function loss due to uniparental disomy abnormalities.
摘要：
■该研究旨在报道LRBA基因中一种新型纯合变体的罕见病例，源于单亲对父系起源的偏见。该病例为LRBA基因变异数据库提供了新的临床数据。
■该研究详细介绍了2023年5月在我们中心诊断为纯合LRBA基因变异的2岁儿童的情况。收集患者的详细临床资料，包括外周血单核细胞的全外显子组测序，父母的遗传验证。
■患儿出现反复呼吸道感染和慢性中性粒细胞减少症，进展为全血细胞减少症.影像学显示腋窝和腹部区域脾肿大和淋巴结肿大。外周血淋巴细胞计数显示B细胞和NK细胞减少。观察到IFN-α和IFN-r的细胞因子水平升高。全外显子组测序揭示了LRBA基因中的无义纯合变体，特别是c.2584C>T（p。Gln862Ter）。父亲在该基因座处表现出杂合变体，而在母亲身上没有发现变异。样本分析表明单亲二体的特征。根据美国医学遗传学和基因组学学院（ACMG）的指导方针，这种变异体被初步归类为“可能致病”。目前,学术文献中没有关于该特定变异位点的报道.
■LRBA基因变异可导致罕见的先天性免疫错误。c.2584C>T（p。LRBA基因外显子22中的Gln862Ter）变体是一种新发现的致病性变体，由单亲二倍体引起的纯合变异极为罕见。该病例代表了由于单亲二体性异常而导致的LRBA基因功能丧失的第二份全球报告。
■该研究详细介绍了2023年5月在我们中心诊断为纯合LRBA基因变异的2岁儿童的情况。收集患者的详细临床资料，包括外周血单核细胞的全外显子组测序，父母的遗传验证。
■患儿出现反复呼吸道感染和慢性中性粒细胞减少症，进展为全血细胞减少症.影像学显示腋窝和腹部区域脾肿大和淋巴结肿大。外周血淋巴细胞计数显示B细胞和NK细胞减少。观察到IFN-α和IFN-r的细胞因子水平升高。全外显子组测序揭示了LRBA基因中的无义纯合变体，特别是c.2584C>T（p。Gln862Ter）。父亲在该基因座处表现出杂合变体，而在母亲身上没有发现变异。样本分析表明单亲二体的特征。根据美国医学遗传学和基因组学学院（ACMG）的指导方针，这种变异体被初步归类为“可能致病”。目前,学术文献中没有关于该特定变异位点的报道.
■LRBA基因变异可导致罕见的先天性免疫错误。c.2584C>T（p。LRBA基因外显子22中的Gln862Ter）变体是一种新发现的致病性变体，由单亲二倍体引起的纯合变异极为罕见。该病例代表了由于单亲二体性异常而导致的LRBA基因功能丧失的第二份全球报告。
