Esposito Maria Valeria, Comegna Marika, Cernera Gustavo, Gelzo Monica, Paparo Lorella, Berni Canani Roberto, Castaldo Giuseppe
CEINGE-Biotecnologie Avanzate, 80145 Naples, Italy.
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Naples, Italy.
Diagnostics (Basel). 2021 Feb 8;11(2):262. doi: 10.3390/diagnostics11020262.
Congenital diarrheal disorders (CDDs) are early-onset enteropathies generally inherited as autosomal recessive traits. Most patients with CDDs require rapid diagnosis as they need immediate and specific therapy to avoid a poor prognosis, but their clinical picture is often overlapping with a myriad of nongenetic diarrheal diseases. We developed a next-generation sequencing (NGS) panel for the analysis of 92 CDD-related genes, by which we analyzed patients suspect for CDD, among which were (i) three patients with sucrose-isomaltase deficiency; (ii) four patients with microvillous inclusion disease; (iii) five patients with congenital tufting enteropathy; (iv) eight patients with glucose-galactose malabsorption; (v) five patients with congenital chloride diarrhea. In all cases, we identified the mutations in the disease-gene, among which were several novel mutations for which we defined pathogenicity using a combination of bioinformatic tools. Although CDDs are rare, all together, they have an incidence of about 1%. Considering that the clinical picture of these disorders is often confusing, a CDD-related multigene NGS panel contributes to unequivocal and rapid diagnosis, which also reduces the need for invasive procedures.
先天性腹泻疾病（CDDs）是早发性肠病，通常作为常染色体隐性性状遗传。大多数CDDs患者需要快速诊断，因为他们需要立即进行特定治疗以避免预后不良，但他们的临床表现常常与众多非遗传性腹泻疾病重叠。我们开发了一个用于分析92个与CDD相关基因的二代测序（NGS）面板，通过该面板我们分析了疑似患有CDD的患者，其中包括：（i）三名蔗糖异麦芽糖酶缺乏症患者；（ii）四名微绒毛包涵体病患者；（iii）五名先天性簇绒性肠病患者；（iv）八名葡萄糖 - 半乳糖吸收不良患者；（v）五名先天性氯化物腹泻患者。在所有病例中，我们都鉴定出了疾病基因中的突变，其中有几个新突变，我们使用生物信息学工具组合确定了它们的致病性。尽管CDDs很少见，但总体发病率约为1%。考虑到这些疾病的临床表现常常令人困惑，一个与CDD相关的多基因NGS面板有助于明确和快速诊断，这也减少了侵入性检查的需求。
