Genetik Testin Değerlendirilmesinde Klinik Bulguların Önemi: Bir Psödo-Gaucher Ailesi

Year 2025, Volume: 12 Issue: 2, 88 - 93, 31.08.2025

Cagri Dogan , Elif Dogan

https://doi.org/10.56941/odutip.1728340

Abstract

Gaucher hastalığı, GBA genindeki patojenik mutasyonlara bağlı olarak glukoserebrozidaz enzim aktivitesinin azalması ya da yokluğu sonucu ortaya çıkan otozomal resesif bir lizozomal depo hastalığıdır. Bu hastalık Tip 1 (non-nöropatik), Tip 2 (akut nöropatik) ve Tip 3 (subakut nöropatik) olmak üzere üç ana forma ayrılır. Tip 1 en sık görülen form olup hepatosplenomegali, anemi, kemik ağrıları ve gelişme geriliği gibi belirtilerle karakterizedir. Bu olgu sunumunda, bilateral diz ve aşil tendon ağrısı ile birlikte ellerde aralıklı his kaybı şikayeti olan 10 yaşındaki bir erkek çocuk ve ailesinin genetik incelemesi sunulmuştur. Ailede daha önce Gaucher tanısı almış bireylerin varlığı nedeniyle Gaucher hastalığı ön tanısı ile genetik analiz yapılmıştır. GBA geninde daha önce raporlanmış iki farklı patojenik mutasyon saptanmış olup, genetik karşılaştırma ile bu mutasyonların aynı allelde (cis) bulunduğu ve olgunun taşıyıcı olduğu anlaşılmıştır. Bulgular, N409S ve V499M mutasyonlarının cis pozisyonda birlikte bulunduğu nadir bir varyasyon kombinasyonunu işaret etmektedir ve bu durumun ülkemize özgü olabileceği düşünülmektedir. Bu çalışma, genetik test sonuçlarının klinik ve biyokimyasal verilerle birlikte bütüncül değerlendirilmesinin tanısal süreçteki önemini vurgulamaktadır.

Keywords

yeni nesil sekanslama , psödegaucher hastalığı , genetik tanı

The Importance of Clinical Findings in the Evaluation of Genetic Testing A Pseudo-Gaucher

Abstract

Gaucher disease is an autosomal recessive lysosomal storage disorder resulting from reduced or absent glucocerebrosidase enzyme activity due to pathogenic mutations in the GBA gene. The disease is classified into three main forms: Type 1 (non-neuropathic), Type 2 (acute neuropathic), and Type 3 (subacute neuropathic). Type 1 is the most prevalent form of the disease and is characterised by clinical features such as hepatosplenomegaly, anemia, bone pain, and growth retardation. In this case report, we present the genetic evaluation of a 10-year-old male patient with bilateral knee and Achilles tendon pain accompanied by intermittent numbness in the hands, as well as his family members is presented. Given the presence of previously diagnosed Gaucher patients within the family, a genetic analysis was performed with a preliminary diagnosis of Gaucher disease. Two previously reported pathogenic mutations in the GBA gene were identified, and comparison of familial genetic data revealed that these mutations were located in cis configuration, indicating that the index case was a carrier, not an affected individual. The findings point to a rare mutational combination of N409S and V499M occurring in cis, which may represent a population-specific pattern in Turkey. This study highlights the critical importance of interpreting genetic testing results in conjunction with clinical and biochemical findings for the accurate diagnosis of genetic disorders.

Keywords

genetic diagnosis , pseudogaucher disease , next generation sequencing

References

• Grabowski GA. Gaucher disease and other storage disorders. Hematology Am Soc Hematol Educ Program. 2012;2012(1):13-8.
• Horowitz M, Wilder S, Horowitz Z, Reiner O, Gelbart T, Beutler E. The human glucocerebrosidase gene and pseudogene: structure and evolution. Genomics. 1989;4(1):87-96.
• Brady RO. Enzymatic basis of Gaucher disease. J Clin Invest. 1965;44(1):20-8.
• Beutler E, Grabowski GA. Gaucher disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001. p. 3635-68.
• Zimran A. How I treat Gaucher disease. Blood. 2011;118(6):1463-71.
• Weinreb NJ, Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease. Am J Med. 2002;113(2):112-9.
• Mistry PK, Sadan S, Yang R, Yee J, Yang M. Gaucher disease: progress and ongoing challenges. Mol Genet Metab. 2011;104(4):443-7.
• Sidransky E. Gaucher disease: insights from a rare Mendelian disorder. Discov Med. 2004;4(20):225-33.
• Haliloglu G, Hopwood JJ, Kobayashi H, Hasiloglu ZI, Saatci I, Coskun T, et al. Clinical and molecular findings in Turkish patients with Gaucher disease. Am J Med Genet A. 2005;136(1):48-53.
• Sidransky E, Sherer DM, Ginns EI. Mutation analysis in Gaucher disease. Am J Hum Genet. 1993;52(6):1094-103.
• Dursun A, Ozgul RK, Gungor O, Sivri S, Tokatli A, Coskun T, et al. Genotype-phenotype correlation in Turkish Gaucher patients. Mol Genet Metab. 2009;97(1):21-6.
• Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, et al. Gaucher disease: recommendations on diagnosis, evaluation, and monitoring. Arch Intern Med. 2000;160(18):2835-43.
• Cox TM. Gaucher disease: clinical profile and therapeutic developments. Biologics. 2010;4:299-313.
• Onal H, Tumer L, Aydin A, Yucel-Yilmaz D, Tumer Z. Molecular genetic analysis of Turkish Gaucher’s disease patients reveals three novel variants in glucocerebrosidase (GBA) gene. Meta Gene. 2020;25:100725. doi:10.1016/j.mgene.2020.100725
• Zimran A, Sorge J, Gross E, Kubitz M, West C, Beutler E. Type 1 Gaucher disease: phenotypic variation and long-term follow-up. Br J Haematol. 1990;75(1):10-6.
• Balwani M, Fuerstman L, Kornreich R, Edelmann L, Desnick RJ. Genotype–phenotype correlations in Gaucher disease: a review of GBA mutations from the Mayo Clinic cohort. Clin Genet. 2020;97(3):586-95. doi:10.1111/cge.13774