Novel TMEM63A mutation associated with transient hypomyelination of infancy - lessons from a previously negative whole-exome sequencing case: Three case reports
Issued Date
2026-01-01
Resource Type
ISSN
22192808
Scopus ID
2-s2.0-105043400880
Journal Title
World Journal of Clinical Pediatrics
Volume
15
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
World Journal of Clinical Pediatrics Vol.15 No.2 (2026)
Suggested Citation
Chanvanichtrakool M., Kulsirichawaroj P., Jaito W., Pho-Iam T., Kamolvisit W., Likasitwattanakul S. Novel TMEM63A mutation associated with transient hypomyelination of infancy - lessons from a previously negative whole-exome sequencing case: Three case reports. World Journal of Clinical Pediatrics Vol.15 No.2 (2026). doi:10.5409/wjcp.v15.i2.117629 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/117853
Title
Novel TMEM63A mutation associated with transient hypomyelination of infancy - lessons from a previously negative whole-exome sequencing case: Three case reports
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
BACKGROUND Hypomyelinating leukodystrophies are rare neurodevelopmental disorders characterized by impaired myelin development and early motor delay. Hypomyelinating leukodystrophy type 19 (HLD-19), also termed transient hypomyelination of infancy, is caused by TMEM63A variants. It can clinically resemble other hypomyelinating leukodystrophies but is distinguished by developmental improvement. However, its phenotypic spectrum remains incompletely defined. CASE SUMMARY We describe 3 related individuals presenting in early infancy with nystagmus, hypotonia, and delayed motor milestones. Brain magnetic resonance imaging demonstrated diffuse hypomyelination, followed by progressive clinical improvement and normalization of myelination on serial imaging. Initial trio whole-exome sequencing was nondiagnostic. Reanalysis-prompted by recognition of additional affected relatives and refinement of human phenotype ontology (HPO) annotation-identified a novel heterozygous TMEM63A variant (c.146G>T; p.Gly49Val). The variant segregated with disease in multiple affected family members. CONCLUSION This familial series expands the clinical and genetic spectrum of TMEM63A-related HLD-19. It emphasizes that whole-exome sequencing reanalysis-particularly when family structure or phenotype evolves and when broader HPO terms are applied-can secure a diagnosis and improve counseling and prognostic guidance.