From prenatal testing to adult rare disease: Scaling genomic analysis in Finland

Speaker: Minna Paavola, Ph.D., Clinical Laboratory Geneticist, Turku University Hospital, Turku, Finland

About this webinar

Whole exome sequencing (WES) presents distinct challenges depending on where in the clinical spectrum it's applied - from fetal phenotypes with limited available data, to longstanding unresolved cases in adults. In this talk presented at ESHG 2026, Minna Paavola shares how the germline rare disease team at Turku University Hospital has built a scalable, consistent WES workflow that spans both ends of that spectrum.

Minna will walk through the lab's end-to-end process - from library preparation using the SOPHiA DDM™ Whole Exome Solution through analysis and variant classification in SOPHiA DDM™, with Alamut™ Visual Plus supporting interpretation - and explain the team's approach to filtering, prioritization, and variant flagging across referral types. The talk also draws on two research cases from the lab's practice: a prenatal trio in which compound heterozygous variants in the GLE1 gene - one a Finnish founder variant for Herva disease - were identified in a fetus presenting with severe fetal akinesia; and an adult solo case resolved after decades, in which biallelic MRE11 variants explained a complex neurological phenotype initially complicated by childhood cerebral palsy. Both cases illustrate how careful attention to population-specific allele frequencies, inheritance patterns, and HPO-guided filtering can surface clinically significant findings that initial automated classification may underweight.

Minna will also discuss the Finnish Disease Heritage - a group of approximately 40 rare monogenic disorders at elevated frequency in Finland due to historical population bottlenecks - and how awareness of founder variants shapes the team's analytical approach.

You will learn:

• How Turku University Hospital structures its WES workflow across referral types, from single-gene requests to complex trios
• The team's prioritization-based filtering approach, including the use of virtual panels and HPO terms in SOPHiA DDM™
• How SOPHiA DDM™ Community data supports variant interpretation
• The role of population-specific allele frequencies - particularly in gnomAD Finnish vs. non-Finnish cohorts - in evaluating variant pathogenicity
• Practical guidance on common pitfalls: missense variants that appear benign, intronic variants with splicing implications, and "common" variants that remain pathogenic in context

SOPHiA DDM™ Exome applications and Alamut™ Visual Plus are For Research Use Only. The opinions expressed are those of the speaker and may not represent the opinions of SOPHiA GENETICS.