Neuroimaging to Genotype: Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population
Document Type
Article
Publication Title
American Journal of Medical Genetics, Part A
Abstract
Several genetic disorders are associated with either a permanent deficit or a delay in central nervous system myelination. We investigated 24 unrelated families (25 individuals) with deficient myelination after clinical and radiological evaluation. A combinatorial approach of targeting and/or genomic testing was employed. Molecular diagnosis was achieved in 22 out of 24 families (92%). Four families (4/9, 44%) were diagnosed with targeted testing and 18 families (18/23, 78%) were diagnosed using broad genomic testing. Overall, 14 monogenic disorders were identified. Twenty disease-causing variants were identified in 14 genes including PLP1, GJC2, POLR1C, TUBB4A, UFM1, NKX6-2, DEGS1, RNASEH2C, HEXA, ATP7A, SETBP1, GRIN2B, OCLN, and ZBTB18. Among these, nine (45%) variants are novel. Fourteen families (82%, 14/17) were diagnosed using proband-only exome sequencing (ES) complemented with deep phenotyping, thus highlighting the utility of singleton ES as a valuable diagnostic tool for identifying these disorders in resource-limited settings.
DOI
10.1002/ajmg.a.63914
Publication Date
1-1-2024
Recommended Citation
Kaur, Namanpreet; do Rosario, Michelle C; Majethia, Purvi; and Mascarenhas, Selinda, "Neuroimaging to Genotype: Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population" (2024). Open Access archive. 10592.
https://impressions.manipal.edu/open-access-archive/10592
