Monogenic mutations in four cases of neonatal-onset watery diarrhea and a mutation review in East Asia.

Background: 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.

Main Body: 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.

Conclusion: 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.