PDF(Pubmed)
Abstract：
Pediatric intestinal pseudo-obstruction (PIPO) is a heterogeneous condition characterized by impaired gastrointestinal propulsion, a broad clinical spectrum, and variable severity. Several molecular bases underlying primary PIPO have been identified, of which autosomal dominant ACTG2-related visceral myopathy is the most common in both familial or sporadic primary PIPO cases. We present a family with autosomal recessive ACTG2-related disease in which both parents have mild gastrointestinal symptoms and sons have severe PIPO and bladder dysfunction.
UNASSIGNED: Clinical genome sequencing was performed on the patients and the mother. Immunohistochemistry was performed on intestinal tissue from the patients to show expression levels of the ACTG2.
UNASSIGNED: Genome sequencing identified a 6.8 kb 2p13.1 loss that includes the ACTG2 gene and a maternally inherited missense variant p.Val10Met in the ACTG2 gene.
UNASSIGNED: This case demonstrates that monoallelic hypomorphic ACTG2 variants may underly mild primary gastrointestinal symptoms, while biallelic mild variants can cause severe diseases. The Deletions of the noncoding ACTG2 exon can be an under-recognized cause of mild gastrointestinal symptoms unidentifiable by exome sequencing, explaining some instances of interfamilial variability with an apparent autosomal dominant inheritance. Genome sequencing is recommended as a genetic work-up for primary or idiopathic PIPO because of genetic heterogeneity.
UNASSIGNED: Clinical genome sequencing was performed on the patients and the mother. Immunohistochemistry was performed on intestinal tissue from the patients to show expression levels of the ACTG2.
UNASSIGNED: Genome sequencing identified a 6.8 kb 2p13.1 loss that includes the ACTG2 gene and a maternally inherited missense variant p.Val10Met in the ACTG2 gene.
UNASSIGNED: This case demonstrates that monoallelic hypomorphic ACTG2 variants may underly mild primary gastrointestinal symptoms, while biallelic mild variants can cause severe diseases. The Deletions of the noncoding ACTG2 exon can be an under-recognized cause of mild gastrointestinal symptoms unidentifiable by exome sequencing, explaining some instances of interfamilial variability with an apparent autosomal dominant inheritance. Genome sequencing is recommended as a genetic work-up for primary or idiopathic PIPO because of genetic heterogeneity.
摘要：
小儿假性肠梗阻(PIPO)是一种以胃肠推进功能受损为特征的异质性疾病,广泛的临床谱，和可变的严重性。已经确定了几个主要PIPO的分子碱基，其中常染色体显性遗传ACTG2相关内脏肌病在家族性或散发性原发性PIPO病例中最常见。我们介绍了一个常染色体隐性遗传ACTG2相关疾病的家庭，其中父母双方都有轻度胃肠道症状，儿子有严重的PIPO和膀胱功能障碍。
■对患者和母亲进行临床基因组测序。对来自患者的肠组织进行免疫组织化学以显示ACTG2的表达水平。
■基因组测序鉴定出6.8kb2p13.1缺失，其中包括ACTG2基因和ACTG2基因中的母系遗传错义变体p.Val10Met。
■该病例表明，单等位基因低态ACTG2变异体可能是轻微的原发性胃肠道症状，而双等位基因轻度变异可引起严重疾病。非编码ACTG2外显子的缺失可能是外显子组测序无法识别的轻度胃肠道症状的公认原因。解释一些具有明显常染色体显性遗传的家族间变异性的实例。由于遗传异质性，建议将基因组测序作为原发性或特发性PIPO的遗传检查。
■对患者和母亲进行临床基因组测序。对来自患者的肠组织进行免疫组织化学以显示ACTG2的表达水平。
■基因组测序鉴定出6.8kb2p13.1缺失，其中包括ACTG2基因和ACTG2基因中的母系遗传错义变体p.Val10Met。
■该病例表明，单等位基因低态ACTG2变异体可能是轻微的原发性胃肠道症状，而双等位基因轻度变异可引起严重疾病。非编码ACTG2外显子的缺失可能是外显子组测序无法识别的轻度胃肠道症状的公认原因。解释一些具有明显常染色体显性遗传的家族间变异性的实例。由于遗传异质性，建议将基因组测序作为原发性或特发性PIPO的遗传检查。
