Genome sequencing analysis of a family with a child displaying severe abdominal distention and recurrent hypoglycemia.

Background Germline mutations in PTEN are associated with the PTEN hamartoma tumor syndrome (PHTS), an umbrella term used to describe a spectrum of autosomal-dominant disorders characterized by variable phenotypic manifestations associated with cell or tissue overgrowth. We report a boy who developed severe progressive abdominal distention due to a dramatic adipose mass from the age of 7 months and developed recurrent hypoinsulinemic hypoglycemia that led to seizures at the age of 4 years. Methods Trio-based whole-genome sequencing was performed by using blood DNA from the child and his parents. The possible pathogenic variants were verified by Sanger sequencing. Functional characterization of the identified variant was completed by western blot. Results The child inherited a single-nucleotide deletion NM_000314.6:c.849delA (p.Glu284Argfs) in the tumor suppressor gene PTEN from his father. The paternal family members have a history of cancer. It is conceivable that PTEN loss-of-function induced the adipose tumor growth and hypoglycemia, although the proband did not meet the usual diagnosis criteria of Cowden syndrome or Bannayan-Riley-Ruvalcaba syndrome that are characterized by germline mutations of PTEN. Conclusion This case underlines the variability of phenotypes associated with PTEN germline mutations and provides useful information for diagnosis and genetic counseling of PTEN-related diseases for pediatric patients.