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

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

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