婴儿突然意外死亡(SUDI)是家庭的创伤事件,不幸的是,它在世界许多地方仍然很高。虽然大多数情况下死因已经解决,其他人在验尸后仍未确定。人们已经认识到基因检测在无法解释的病例中的作用,以前的研究已经通过DNA分析证明了病例的分辨率。在这里,我们介绍了两个在盐河太平间住院的SUDI病例的病例报告,南非,并显示使用临床外显子组测序确定了两名婴儿的潜在死亡原因。第一个婴儿是COL6A3中变体(rs148175795)的杂合子,这表明支气管肺发育不良表型。这一假设导致在DMP1中发现了第二个候选变体(rs142880465),这可能有助于更严重表型的双基因/多基因机制。保留组织切片的组织学分析显示窒息死亡机制,潜在的支气管肺发育不良引起的细支气管肌无力可能通过影响呼吸而导致窒息。在第二个婴儿中,在MASP1中鉴定了纯合变体(rs201340753),该变体在每个亲本中都是杂合的,强调在遗传研究中包括亲本DNA的价值。虽然无法评估甘露糖结合凝集素缺乏症,这种变异可能与三重风险模型中的其他风险因素共同作用,导致猝死,这是合理的.这些结果可能对家庭成员有遗传影响,并代表分子尸检可能的新候选变体。
Sudden unexpected death in infants (SUDI) is a traumatic event for families, and unfortunately its occurrence remains high in many parts of the world. Whilst cause of death is resolved for most cases, others remain undetermined following postmortem investigations. There has been a recognition of the role of genetic testing in unexplained cases, where previous studies have demonstrated the resolution of cases through DNA analyses. Here we present two
case reports of SUDI cases admitted to Salt River Mortuary, South Africa, and show that underlying causes of death were determined for both infants using clinical exome sequencing. The first infant was heterozygous for a variant (rs148175795) in COL6A3, which suggested a bronchopulmonary dysplasia phenotype. This hypothesis led to finding of a second candidate variant in DMP1 (rs142880465), which may contribute towards a digenic/polygenic mechanism of a more severe phenotype. Histological analysis of retained tissue sections showed an asphyxial mechanism of death, where bronchiolar muscle weakness from an underlying bronchopulmonary dysplasia may have contributed to the asphyxia by affecting respiration. In the second infant, a homozygous variant (rs201340753) was identified in MASP1, which was heterozygous in each parent, highlighting the value of including parental DNA in genetic studies. Whilst mannose-binding lectin deficiency could not be assessed, it is plausible that this variant may have acted in combination with other risk factors within the triple-risk model to result in sudden death. These results may have genetic implications for family members, and represent possible new candidate variants for molecular autopsies.