|Title||Genome sequencing analysis of a family with a child displaying severe abdominal distention and recurrent hypoglycemia.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Liu, J, Ding, G, Zou, K, Jiang, Z, Zhang, J, Lu, Y, Pignata, A, Venner, E, Liu, P, Liu, Z, Wangler, MF, Sun, Z|
|Journal||Mol Genet Genomic Med|
|Date Published||2020 03|
|Keywords||Abdominal Neoplasms, Child, Preschool, Humans, Hypoglycemia, Loss of Function Mutation, Male, Neoplasms, Adipose Tissue, Pedigree, Phenotype, PTEN Phosphohydrolase, Seizures, Syndrome|
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.
|Alternate Journal||Mol Genet Genomic Med|
|PubMed Central ID||PMC7057095|
|Grant List||P30 ES030285 / ES / NIEHS NIH HHS / United States |
P30 DK056338 / DK / NIDDK NIH HHS / United States
P50 CA126752 / CA / NCI NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States