Neuroimaging to Genotype: Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population

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.