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

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.