Paternal UPD (15) With Disease-Causing Mutation and Small Supernumerary Ring Chromosome 15: A Case Report.

Area of Science:

• Genetics
• Genomic imprinting
• Epigenetics

Background:

• Uniparental disomy (UPD) is an unusual inheritance pattern where an individual inherits two copies of a chromosome from only one parent.
• This can disrupt normal gene function and lead to various phenotypic abnormalities.
• Bartter syndrome Type 1 is a genetic disorder affecting kidney function.

Observation:

• A patient with Bartter syndrome Type 1 was identified.
• The condition was linked to a homozygous pathogenic variant in the SLC12A1 gene.
• This variant was unmasked by mosaic paternal UPD of chromosome 15.

Findings:

• The patient's genetic makeup suggests a trisomy rescue event, leading to two distinct cell lines.
• This event also unmasked a pathogenic paternal SLC12A1 variant, causing Bartter syndrome Type 1.
• A maternally derived ring chromosome 15 influenced nondisjunction and UPD, contributing to the unique etiology.

Implications:

• This case highlights the role of trisomy rescue and paternal UPD in revealing recessive genetic variants.
• It underscores the complex mechanisms underlying genetic disorders.
• Understanding these mechanisms is crucial for accurate diagnosis and genetic counseling.