Spectrum of neuro‐genetic disorders in the United Arab Emirates national population

Abstract

Clinical and molecular characterization of neuro‐genetic disorders among UAE national patients seen in the Genetic Clinic at Tawam hospital over a period of 3\u2009years. A retrospective chart review of all Emirati patients assessed by clinical geneticists due to neuro‐genetic disorders including global developmental delay, ASD, ID, ADHD, and epilepsy in combination with abnormalities of other organ systems. Each patient had proper assessment including detailed history, three‐generation family history, developmental history and detailed physical examination looking for other system involvement. Hearing test and ophthalmological examination were performed when needed. Magnetic resonance imaging (MRI) of the brain, echocardiogram, and renal ultrasound were pursued as indicated. Detailed psychological evaluation and psychometric assessment were done when indicated. The review was done for a period between January 2018 and December 2020. Genetic investigations included chromosome karyotype, FISH study, metabolic/biochemical tests, chromosome microarray, gene sequencing, targeted mutation testing, trio whole exome and trio genome sequencing. A total of 644 patients with developmental delay, ID, learning difficulty, ASD, ADHD, or NNDs, were seen in genetic clinic from January 2018 to December 2020. A total of 506 patients were included in this review, all completed the genetic evaluations during the study period. There were 398 (61.8%) males and 246 (38.2%) females, with a ratio of 1.6:1. Positive family history of NDD was documented in 132 families, while 115 families had negative history and family history was unknown/unclear in the remaining. Fifty seven (11.26% [57/506]) patients had positive microarray results. Hundred ninety seven (38.9% [197/506]) patients had positive molecular testing. Genetic disorders were found in 133 (67.5% [133/197]) and inborn errors of metabolism were found in 42 (21.3% [42/197]). Consanguinity was documented in 139 patients with positive molecular diagnoses (139/197, 70.5%). Sixty nine (35% [69/197]) patients had autosomal dominant disorders, majority were De Novo (84%). Ninety‐five (48% [95/197]) patients had autosomal recessive diseases, 40 mutations involved inborn errors of metabolism and 50 mutations involved genetic disorders. Pathogenic variants causing both autosomal dominant and recessive disorders were found in 98 patients (49.7% [98/197]), likely pathogenic variants causing both autosomal dominant and recessive disorders were found in 66 patients (33.5% [66/197]). X‐linked related disorders were found in 10 patients (5% [10/197]). Mitochondrial mutation was found in one patient. Novel mutations were found in 76 patients (76/197 i.e., 38.56%). Twenty two patients had variants of unknown significant. The remaining 252 studied patients (252/506 i.e., 49.8%), remained undiagnosed. This study shows that neuro‐genetic disorders in the UAE are very heterogeneous at clinical and molecular levels. Using microarray, WES and WGS a diagnosis was reached in 50% of the patients while no diagnosis was reached in other half of the studied patients. It is possible that some mutations were missed by WGS and WES. However, it is also possible that many of disorders in UAE population are novel and the causative mutation is not yet discovered. More researches need to be done in this population to uncover the molecular basis of these disorders.