Recent Advances in Cytogenomics for Genetic Diagnosis in the Center of Excellence for Human Genetics in Egypt

Mohamed, Amal; Eid, Maha M.; Mekkawy, Mona K; Eid, Ola M.; Abd-Elnaby, Azza E; Zaki, Maha S; Ashaat, Engy; Abdel-Salam, Ghada M; Aglan, Mona; Issa, Mahmoud; Mahmoud, Wael; Elgerzawy, Assad; Hassan, Shymaa; Abdalla, Sally; Sayed, Engy S; Erian, Peter S; Mahrous, Rana; Madian, Abdelrahman; Refaat, Khaled; Abdel Kader, Rania M; Farid, Marwa; Khedr, Azzah; Shihab, Marwa; Kayed, Hesham; Fadel, Islam; Helmy, Nivine; Kamel, Alaa K

doi:10.21608/mxe.2024.334495.1034

Recent Advances in Cytogenomics for Genetic Diagnosis in the Center of Excellence for Human Genetics in Egypt

Document Type : Original Article

Authors

¹ National Research Centre

² El Buhouth street , Dokki

10.21608/mxe.2024.334495.1034

Abstract

Background: This study aimed to apply the recent advances in cytogenomic techniques in diagnosing genetic disorders for proper genetic counseling. This work was done in the Centre of Excellence of Human Genetics, National Research Centre, Egypt. The center is funded by the STDF (project 5253).
Methods: The total number of referral patients was 2170 from 2016 to 2020. The Cytogenetic Team performed different cytogenomic techniques for four clinical genetics clinics: Neurodevelopment group, Hereditary blood group, Limb Malformation/Skeletal dysplasia group, and Multiple Congenital anomalies group. Karyotype was done for all patients, Fluorescence in situ hybridization (FISH) was performed for 324 patients, multiplex ligation-dependent probe amplification (MLPA) was performed for 160 patients, and array CGH for 90 patients. We followed the European guidelines for constitutional cytogenomic analysis in all applied techniques.
Results: Chromosomal abnormalities were detected in 6.6% of the referred patients (Down syndrome was excluded). Using FISH analysis, 226 patients were diagnosed with microdeletion syndromes and 98 with chromosomal abnormalities or marker chromosomes. MLPA technique was performed for 160 patients who had intellectual disability/multiple congenital abnormalities (ID/MCA). We used a probe mix for MR, subtelomere, and microdeletion syndromes. 26 patients (16%) had positive results. Array CGH was performed for 90 patients, out of them 44(49%) had large copy number variations. Some of these copy number variations involved two chromosomes or complex rearrangements. Negative patients were referred for whole exome sequencing.
Conclusion: The cytogenomic techniques could increase the number of accurately diagnosed patients. The array CGH is the first tier for the diagnosis of the genetic causes of ID/MCA and could allow accurate genotype/phenotype correlation. Proper genetic diagnoses are important for genetic counseling.

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