SPECTRUM OF TARGETED MOLECULAR GENETIC TESTING RESULTS FOR SPINK1, PRSS1, CFTR, BRCA1, AND BRCA2: A PILOT DESCRIPTIVE STUDY

Relevance. Genetic factors play an important role in determining individual susceptibility to pancreatic diseases. Variants in SPINK1, PRSS1, and CFTR are associated with different forms of pancreatitis, whereas BRCA1 and BRCA2 are primarily relevant in the context of hereditary cancer predisposition. Evaluation of molecular genetic testing results in clinical practice may help characterize the spectrum of genetic findings and inform future clinical genetic research.

Objective. To describe the spectrum and frequency of molecular genetic testing results for SPINK1, PRSS1, CFTR, BRCA1, and BRCA2 in a pilot clinical series, with separate analyses at the level of unique patients and individual genetic tests.

Materials and Methods. A pilot retrospective descriptive study was conducted among patients evaluated at Medcenter-Rakhat LLP, Almaty, Republic of Kazakhstan, in 2021-2022. The analysis included 14 unique patients and the results of 16 molecular genetic tests: SPINK1, n = 5; PRSS1, n = 2; CFTR, n = 5; and BRCA1/BRCA2, n = 4. Analyses were performed separately at the patient and individual-test levels. Categorical variables are presented as n (%). Exact two-sided 95 % confidence intervals (CIs) for proportions were calculated using the Clopper–Pearson method. Statistical analyses were performed using R version 4.5.2.

Results. Findings interpreted in the original laboratory reports as being associated with increased susceptibility to pancreatitis were identified in 2 of 14 patients (14.3 %; 95 % CI, 1.8–42.8 %). In both cases, a heterozygous SPINK1 p.Asn34Ser (N34S) variant was identified. Among the five SPINK1 tests, this variant was detected in 2 cases (40.0 %; 95 % CI, 5.3–85.3 %). No other risk-associated findings were reported for PRSS1, CFTR, or BRCA1/BRCA2 according to the original laboratory interpretations.

Conclusions. In this pilot clinical series, the heterozygous SPINK1 p.Asn34Ser variant was the only risk-associated genetic finding identified. The small sample size and heterogeneity of genetic testing limit the generalizability of the findings and support the need for larger studies using standardized genetic testing and systematic evaluation of genotype–phenotype associations.

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