Journal article
Congenital muscle dystrophies: Role of singleton whole exome sequencing in countries with limited resources
Clinical neurology and neurosurgery, Vol.217, pp.107271-107271
06/2022
DOI: 10.1016/j.clineuro.2022.107271
PMID: 35533453
Abstract
Identify the genetic determinants of congenital muscle dystrophy (CMD) in Jordanian children.
This prospective study included patients suspected to have CMD. Singleton whole-exome sequencing (WES) was performed as the first-tier diagnostic test.
44 patients were included: 27 boys and 17 girls. Consanguinity was reported in 32/44 (72.7%) patients, and a positive family history in 16/44 (36.3%) patients.
WES uncovered pathogenic/ likely pathogenic variants in 19/44 (43.1%) patients, variants of uncertain significance (VUS) and negative results were identified in 15/44 (34.0%) and 10/44 (22.7%) patients respectively.
Variants related to CMD were identified in 23/44 (52.2%) patients; pathogenic /likely pathogenic variants were identified in 12/23 (52.1%) and VUS in 11/23 (47.8%). The most common genes were related to basal membrane/extracellular proteins followed by genes related to alpha‑dystroglycanopathies. We have identified a rare association of one family with one sibling affected by CMD and the other sibling with Duchenne muscle dystrophy. A history suggestive of perinatal insult was found in 6/23 (26.0%) patients necessitating a high index of suspicion as CMD may present as cerebral palsy mimickers.Several strong candidate VUSs were identified and need future second tier testing for confirmation.
WES identified genes related to other neuromuscular and non neuromuscular disorders in 21/44 (47.7%) patients;7/21 were pathogenic/likely pathogenic and 14/21 (66.6%) were VUS.
In countries with limited resources singleton WES could be considered the first tier diagnostic test to limit costs.
•Congenital muscular dystrophies overlap with other neuromuscular disorders.•Some patients might have a history suggestive of perinatal insult.•Applying singleton whole exome sequencing can diagnose half of the patients.•When resources are limited, singleton whole exome sequencing decreases costs.
Details
- Title: Subtitle
- Congenital muscle dystrophies: Role of singleton whole exome sequencing in countries with limited resources
- Creators
- Amira T. Masri - University of JordanLiyana Oweis - University of JordanAbdelkarim Al Qudah - University of JordanHatem El-Shanti - University of Iowa Health Care
- Resource Type
- Journal article
- Publication Details
- Clinical neurology and neurosurgery, Vol.217, pp.107271-107271
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.clineuro.2022.107271
- PMID
- 35533453
- ISSN
- 0303-8467
- eISSN
- 1872-6968
- Grant note
- DOI: 10.13039/501100005712, name: University of Jordan
- Language
- English
- Date published
- 06/2022
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984353944002771
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