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 years. 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

Spectrum of Genetic Disorders and Gene Variants in the United Arab Emirates National Population: Insights from the CTGA Database

“…The latter category includes disorders such as Nonsyndromic Macular Pseudocoloboma, ITFG2 Associated Neurodevelopmental Disorder, and BMPR1A-Related Syndrome. In addition to these novel associations in Table 1, the database also documents neurodevelopmental disorders with unconfirmed causal gene associations, such as those reported for MAP3K9 and ASB11 (Saleh et al, 2021) as well as large chromosomal duplication and deletion syndromes (Alabdullatif et al, 2017).…”

“…With the advent and ease of access to technologies such as Whole Exome Sequencing (WES) and gene panel sequencing, diagnostic rates of genetic disorders have increased significantly (Vaisitti et al, 2021; Sanchez-Luquez et al, 2022; Moundir et al, 2023). In fact, within our set of genetic disorders reported in the UAE, a significant portion comes from the utilization of such high-throughput sequencing techniques on fairly large patient populations (Al-Shamsi et al, 2016; Alsamri et al, 2020; Mahfouz et al, 2020; Saleh et al, 2021). Additionally, UAE has recently prioritized research on clinical genetics and the inclusion of genetics in the country’s health priorities.…”

“…Similarly, In five unrelated Emirati families with Ehlers-Danlos Syndrome, Type VI (OMIM# 225400), the same causal NM_000302.4:c.955C>T mutation was seen on a shared haplotype (Giunta et al, 2005). In three separate Emirati tribes, the NM_198535.2:c.436_439del deletion was found to be associated with DECCAGS Syndrome (Saleh et al, 2021). And finally, in a remarkable example, in two UAE tribes, one originating from Oman and one from Yemen, the same NM_001127671.2:c.653dup mutation in the LIFR gene was found in 50 children from 28 families with Stuve-Wideman syndrome (OMIM# 601559) (Al-Gazali and Hamamy, 2014).…”

Whole Exome Sequencing Achieved a Definite Diagnosis of Kaufman Oculocerebrofacial Syndrome in a Bahraini Family: A Case Report

“…12 Meanwhile in the United Arab Emirates, 1 case of a 9-year-old boy was noted as part of a retrospective analysis on neuro-genetic disorders patients, as well as mentioning that his sibling and cousin were affected. 13 Most cases discussed in the literature allude to the disease being more common in females, 10,12 -14 but no studies confirm that gender has a significant correlation with the syndrome.…”

Mutation spectrum of non‐syndromic hearing loss in the UAE, a retrospective cohort study and literature review

“…A recent systematic review paper about the genetic epidemiology of hearing loss in the 22 Arab countries reported that the incidence of HHL in the captured studies ranged from 1.20 to 18 per 1000 births per year, and the prevalence was the highest in Iraq (76.3%) and the lowest in Jordan (1.5%) (Sidenna et al, 2019). Due to the high consanguinity rate among the UAE population (54%) (Saleh et al, 2021), the number of novel or recurrent mutations in rare deafness genes along with variable genotype-phenotype of hearing loss severity is expected.…”