Case report reveals a pathogenic PTEN splice-site variant in a child with macrocephaly, highlighting the value of transcript analysis for early diagnosis and tumor surveillance.
Key Points
To identify the underlying genetic cause of macrocephaly and developmental delay in a pediatric patient using exome and transcript sequencing.
Evaluated a three-year-old girl presenting with macrocephaly and mild developmental delay after negative findings on chromosomal microarray and NSD1 testing.
Performed whole-exome sequencing followed by reverse transcription-polymerase chain reaction, TA cloning, and Sanger sequencing to characterize the functional impact of an identified PTEN splice-site variant.
Identified a heterozygous splice-site variant in PTEN (NM_000314.8:c.802-1G>A).
Transcript analysis revealed an aberrant transcript lacking the first nucleotide at the 5′ end of exon 8, confirming a loss-of-function effect and establishing a diagnosis of PTEN hamartoma tumor syndrome.