Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank.
Inherited metabolic disorders
Middle Eastern population
VUS reclassification
carrier frequency
inbreeding coefficient
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
13 Sep 2024
13 Sep 2024
Historique:
received:
28
03
2024
revised:
10
09
2024
accepted:
10
09
2024
medline:
17
9
2024
pubmed:
17
9
2024
entrez:
17
9
2024
Statut:
aheadofprint
Résumé
To date, approximately 1,400 inherited metabolic disorders (IMDs) have been described, some of which are treatable. It is estimated that 2-3% of live births worldwide are affected by treatable IMDs. Roughly 80% of IMDs are autosomal recessive, leading to a potentially higher incidence in regions with high consanguinity. The study utilized genome sequencing (GS) data from 14,060 adult Qatari participants who were recruited by the Qatar Biobank (QBB) and sequenced by the Qatar Genome Program (QGP). The GS data was analysed for 125 nuclear genes known to be associated with 115 treatable IMDs. Our study identified 253 pathogenic/likely pathogenic SNVs associated with 69 treatable IMDs, including 211 known and 42 novel predicted loss-of-function variants. We estimated that approximately 1 in 13 unrelated individuals (8%) carry a heterozygous pathogenic variant for at least one of 46 treatable IMDs. Notably, phenylketonuria/hyperphenylalaninemia and homocystinuria had among the highest carrier frequencies (1 in 68 and 1 in 85, respectively). Population-based studies of treatable IMDs, particularly in globally under-studied populations, can identify high-frequency alleles segregating in the community and inform public health policies, including carrier and newborn screening.
Sections du résumé
BACKGROUND
BACKGROUND
To date, approximately 1,400 inherited metabolic disorders (IMDs) have been described, some of which are treatable. It is estimated that 2-3% of live births worldwide are affected by treatable IMDs. Roughly 80% of IMDs are autosomal recessive, leading to a potentially higher incidence in regions with high consanguinity.
METHODOLOGY
METHODS
The study utilized genome sequencing (GS) data from 14,060 adult Qatari participants who were recruited by the Qatar Biobank (QBB) and sequenced by the Qatar Genome Program (QGP). The GS data was analysed for 125 nuclear genes known to be associated with 115 treatable IMDs.
RESULTS
RESULTS
Our study identified 253 pathogenic/likely pathogenic SNVs associated with 69 treatable IMDs, including 211 known and 42 novel predicted loss-of-function variants. We estimated that approximately 1 in 13 unrelated individuals (8%) carry a heterozygous pathogenic variant for at least one of 46 treatable IMDs. Notably, phenylketonuria/hyperphenylalaninemia and homocystinuria had among the highest carrier frequencies (1 in 68 and 1 in 85, respectively).
CONCLUSION
CONCLUSIONS
Population-based studies of treatable IMDs, particularly in globally under-studied populations, can identify high-frequency alleles segregating in the community and inform public health policies, including carrier and newborn screening.
Identifiants
pubmed: 39286960
pii: S1098-3600(24)00202-8
doi: 10.1016/j.gim.2024.101268
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101268Investigateurs
Said I Ismail
(SI)
Wadha Al-Muftah
(W)
Radja Badji
(R)
Hamdi Mbarek
(H)
Dima Darwish
(D)
Tasnim Fadl
(T)
Heba Yasin
(H)
Maryem Ennaifar
(M)
Rania Abdellatif
(R)
Fatima Alkuwari
(F)
Muhammad Alvi
(M)
Yasser Al-Sarraj
(Y)
Chadi Saad
(C)
Asmaa Althani
(A)
Eleni Fethnou
(E)
Fatima Qafoud
(F)
Eiman Alkhayat
(E)
Nahla Afifi
(N)
Sara Tomei
(S)
Wei Liu
(W)
Stephan Lorenz
(S)
Najeeb Syed
(N)
Hakeem Almabrazi
(H)
Fazulur Rehaman Vempalli
(FR)
Ramzi Temanni
(R)
Tariq Abu Saqri
(TA)
Mohammedhusen Khatib
(M)
Mehshad Hamza
(M)
Tariq Abu Zaid
(TA)
Ahmed El Khouly
(A)
Tushar Pathare
(T)
Shafeeq Poolat
(S)
Rashid Al-Ali
(R)
Omar Albagha
(O)
Souhaila Al-Khodor
(S)
Mashael Alshafai
(M)
Ramin Badii
(R)
Lotfi Chouchane
(L)
Xavier Estivill
(X)
Khalid A Fakhro
(KA)
Hamdi Mbarek
(H)
Younes Mokrab
(Y)
Jithesh V Puthen
(JV)
Karsten Suhre
(K)
Zohreh Tatari
(Z)
Informations de copyright
Copyright © 2024. Published by Elsevier Inc.