Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, People's Republic of China.
Orphanet J Rare Dis. 2021 Sep 9;16(1):383. doi: 10.1186/s13023-021-01995-y.
Infants with neonatal-onset diarrhea present with intractable diarrhea in the first few weeks of life. A monogenic mutation is one of the disease etiologies and the use of next-generation sequencing (NGS) has made it possible to screen patients for their mutations.
We retrospectively reviewed the clinical data of four children from unrelated families, who presented with neonatal-onset, chronic, watery, non-bloody diarrhea. After genetic whole-exome sequencing, novel mutations were identified in the EPCAM gene of two children. Congenital chloride diarrhea was diagnosed in one case, which was associated with an SLC26A3 mutation, in which the patient presented with watery diarrhea, malnutrition, and hypochloremic alkalosis. Patient 4 was diagnosed with microvillus inclusion disease and possessed novel compound heterozygous mutations in the MYO5B gene. A review of the genetic variants of SLC26A3 reported in East Asia revealed that c.269_270 dupAA (p.G91Kfs*3) is the most frequent SLC26A3 mutation in China, compared with c.2063-1 G > T in Japan and Korea. EPCAM and MYO5B genetic variants were only sporadically reported in East Asia.
This study expands our knowledge of the clinical manifestations and molecular genetics of neonatal-onset watery diarrhea. Early diagnosis could be achieved by genomic analysis in those infants whose histology features are not typical. The discovery of four novel mutations in the EPCAM gene and two novel mutations in the MYO5B gene provides further etiological evidence for the association of genetic mutations with neonatal-onset diarrhea. To date, c.269_270 dupAA is the most frequent SLC26A3 mutation in China.
新生儿起病腹泻的婴儿在生命的最初几周表现出难治性腹泻。单基因突变为疾病病因之一，下一代测序（NGS）的使用使得对患者的突变进行筛查成为可能。
我们回顾性分析了来自 4 个无亲缘关系家庭的 4 名儿童的临床资料，这些儿童均表现为新生儿起病、慢性、水样、非血性腹泻。对全外显子组进行基因测序后，在 2 名儿童的 EPCAM 基因中发现了新的突变。1 例患儿诊断为先天性氯性腹泻，与 SLC26A3 突变相关，患儿表现为水样腹泻、营养不良和低氯性碱中毒。4 号患儿诊断为微绒毛包涵体病，携带 MYO5B 基因的新型复合杂合突变。对东亚地区 SLC26A3 基因突变的综述显示，与日本和韩国的 c.2063-1 G > T 相比，c.269_270 dupAA（p.G91Kfs*3）是中国最常见的 SLC26A3 突变。EPCAM 和 MYO5B 基因突变在东亚地区仅零星报道。
本研究扩展了我们对新生儿起病水样腹泻临床表现和分子遗传学的认识。对于组织学特征不典型的婴儿，通过基因组分析可以早期诊断。在 EPCAM 基因中发现了 4 个新突变，在 MYO5B 基因中发现了 2 个新突变，为遗传突变与新生儿起病腹泻的相关性提供了进一步的病因学证据。迄今为止，c.269_270 dupAA 是中国最常见的 SLC26A3 突变。
