TY - JOUR
T1 - Neuroimaging to Genotype
T2 - Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population
AU - Kaur, Namanpreet
AU - do Rosario, Michelle C
AU - Majethia, Purvi
AU - Mascarenhas, Selinda
AU - Rao, Lakshmi Priya
AU - Nair, Karthik Vijay
AU - Hunakunti, Bhagesh
AU - Prasannakumar, Adarsh Pooradan
AU - Naik, Rohit
AU - Narayanan, Dhanya Lakshmi
AU - Nayak, Shalini S
AU - Bhat, Vivekananda
AU - Sharma, Suvasini
AU - Ramesh Bhat, Y.
AU - Yatheesha, B. L.
AU - Kulkarni, Rajesh
AU - Patil, Siddaramappa J
AU - Nampoothiri, Sheela
AU - Siddiqui, Shahyan
AU - Girisha, Katta Mohan
AU - Bielas, Stephanie
AU - Shukla, Anju
N1 - Publisher Copyright:
© 2024 Wiley Periodicals LLC.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85208045355
UR - https://www.scopus.com/pages/publications/85208045355#tab=citedBy
U2 - 10.1002/ajmg.a.63914
DO - 10.1002/ajmg.a.63914
M3 - Article
AN - SCOPUS:85208045355
SN - 1552-4825
VL - 197
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 3
M1 - e63914
ER -