Konjenital Anomalisi ve Dismorfik Özellikleri olan Hastalarda Kromozomal Mikroarray Analizinin Tanısal Değeri; 2q33 delesyonu olan İki Yeni Hastanın Ayrıntıları

Öz

Amaç: Moleküler karyotipleme yoluyla kopya sayısı varyasyonlarının (CNV'ler) tespiti, dismorfik özellikler ve birden fazla konjenital anomali (MCA) ile ilişkili genetik anomalileri ortaya çıkarmak için kullanışlıdır. Bu çalışma, belirli fenotipe sahip hastalarda kromozomal mikrodizin analizinin tanısal oranını göstermekte ve çok nadir CNV'lere sahip yeni hastaları sunarak literatüre katkıda bulunmaktadır. Gereç ve Yöntemler: Dismorfik özellikler ve birden fazla konjenital anomaliye sahip 419 hastada kromozomal mikrodizin analizi gerçekleştirildi. Bulgular: Toplamda 50 hastada (%12) 61 CNV tespit edildi. Bu hastalardan ikisinde 2q33.1 delesyonu saptandı. Hasta 13 konuşma gecikmesi, nöbetler, davranış bozuklukları ve SATB2 genini bozan 469 kbp delesyon ile kendini gösterirken; hasta 14, immün yetmezlik, büyüme geriliği, hipotiroidizm, ishal, inmemiş testisler ve alopesi, tırnak displazisi ve oligodonti gibi ektodermal özellikler sergiledi. Bu hastada, 2q33.1q34 bölgesinde CTLA4 genini içeren ve immün yetmezlik belirtilerine neden olan 7.5 Mb delesyon mevcuttu. CASP10 geni ise delesyon bölgesinde yer almamaktadır. Sonuç: Çalışmamıza göre, CTLA4 ve CASP10 genlerinin birlikte delesyonu bağışıklık yetmezliği gibi fenotipik etkilere yol açmaz iken, yalnızca CTLA4 geninin delesyonu hipogamaglobulinemi ve bağışıklık yetmezliği ile sonuçlanabilir. Bu bulgular, moleküler karyotiplemenin nadir CNV'lerin tanısında ve doğumsal anomalileri olan hastaların klinik yönetiminde değerli bir araç olabileceğini göstermektedir. CTLA4 gibi spesifik gen delesyonlarının belirlenmesi, bağışıklık düzenleyici tedaviler de dahil olmak üzere kişiselleştirilmiş tedavi yaklaşımlarına kapı açabilir ve etkilenen ailelerde genetik danışmanlık için önemli bilgiler sağlayabilir.

Anahtar Kelimeler

• Konjenital anomali
• dismorfik bulgular
• moleküler karyotipleme
• 2q33.1 delesyonu
• kromozomal mikrodizin

DIAGNOSTIC VALUE OF CHROMOSOMAL MICROARRAY ANALYSIS IN PATIENTS WITH CONGENITAL ANOMALIES AND DYSMORPHIC FEATURES; DETAILS OF TWO NEW PATIENTS WITH 2q33 DELETIONS

Öz

Objective: Detection of copy number variations (CNVs) through molecular karyotyping is a useful method to assess the genetic anomalies with dysmorphic features and multiple congenital anomalies. This study demonstrated the diagnostic rate of chromosomal microarray analysis in patients with specific phenotype, and also contributed the literature with presenting new patients with very rare CNVs. Material and Methods: Chromosomal microarray analysis was performed in 419 patients with dysmorphic features and multiple congenital anomalies. Results: A total of 61 CNVs were detected in 50 patients (12%). Two of these patients exhibited a 2q33.1 deletion. While patient 13 presented with speech delay, seizures, behavioral abnormalities, and a 469 kbp deletion disrupting SATB2, patient 14 displayed immune deficiency, failure to thrive, hypothyroidism, diarrhea, cryptorchidism, and ectodermal features such as alopecia, nail dysplasia, and oligodontia. This patient had a 7.5 Mb deletion on 2q33.1q34, which included CTLA4 and was responsible for the immune deficiency symptoms of the patient. The CASP10, was not included in the deletion region. Conclusions: According to our study, co-deletion of CTLA4 and CASP10 did not lead to phenotypic effects like immune deficiency. Rather, only the deletion of the CTLA4 gene may result in hypogammaglobulinemia and immune deficiency. These findings suggest that chromosomal microarray analysis can be a valuable tool in diagnosing rare CNVs and guiding clinical management, particularly in patients with immune deficiency and other congenital anomalies. Identifying specific gene deletions, such as CTLA4, may inform personalized treatment approaches, including immune-modulating therapies, and provide insights for genetic counseling in affected families.

Anahtar Kelimeler

• Congenital anomaly
• dysmorphic features
• molecular karyotyping
• 2q33.1 deletion
• chromosomal microarray

Kaynakça

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