The genomic landscape of rare disorders in the Middle East

Genome Medicine

Research

Ruba Rizk¹  Mohamed AlAwadhi²  Abdulla AlKhayat²  Sathishkumar Ramaswamy³  Nour Halabi³  Maha El Naofal³  Roudha Alfalasi³  Sawsan Yaslam³  Ruchi Jain³  Alan Taylor³  Shruti Shenbagam³  Ahmad N. Abou Tayoun⁴  Roberto Di Donato⁵  Fatma Rabea⁶  Alawi Alsheikh-Ali⁷  Shiva Shankar⁸  Munira Al Maazmi⁸  Hamda Abulhoul⁹  Mohamed El Bitar^1,10  Safeena Kherani^1,10  Nandu Thalange^1,11  Arif O. Khan^1,12  Christos Tzivinikos^1,13  Ahmed Nugud^1,14  Ali Alsarhan^1,14  Fatima Sarfraz^1,14  Hiba Janbaz^1,14  Lemis Yavuz^1,14  Deena Wafadari^1,14  Corina Gonzalez^1,15  Walid Abuhammour^1,16  Martin Bitzan^1,17  Ammar AlBanna^1,18  Meshal Sultan^1,18  Alexandra F. Freeman^1,19  Zeinab Alloub^2,20  Mohamed O. E. Babiker^2,21  Nidheesh Chencheri^2,21  Haitham Elbashir^2,22  Sattar Alshryda^2,23  Ibrar Majid^2,23  Hisham Hamdan^2,24 

[1] Adolescent Medicine, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Al Jalila Genomics Center of Excellence, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Al Jalila Genomics Center of Excellence, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Center for Genomic Discovery, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates;Cardiology Department, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates;College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates;Dubai Health Authority, Dubai, United Arab Emirates;Critical Care Centre of Excellence, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Department of Metabolic Medicine, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;ENT Department, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Endocrinology Department, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates;Gastroenterology Department, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;General Pediatrics Department, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Immune Deficiency Cellular Therapy Program, National Cancer Institute, NIH, Bethesda, MD, USA;Infectious Diseases Department, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Kidney Center of Excellence, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Mental Health Center of Excellence, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA;Neurodevelopment Section, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Neurology Department, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Neuroscience Center of Excellence, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Orthopedics Department, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;Pulmonology and Sleep Medicine Department, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates;

关键词: Genomics;    Rare diseases;    Whole-exome sequencing;    Middle East;    Diagnostic yield;    Clinical utility;   

DOI  :  10.1186/s13073-023-01157-8

 received in 2022-09-02, accepted in 2023-01-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans.MethodsWe established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P < .05 was considered statistically significant.ResultsWe present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7–35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7–37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders.ConclusionsEarly access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population.

【 授权许可】

CC BY   
© The Author(s) 2023

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