Novel Gene Mutation Variant in Hypomyelinating Leukodystrophy-8: A Case Report
The incidence of hypomyelinating leukodystrophies is approximately 1 in every 250,000–500,000 individuals in the population. Hypomyelinating leukodystrophy-8 (HLD-8) is characterized by classical clinical features, including modest intellectual deficits and early-onset progressive cerebellar ataxia,...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2024-11-01
|
| Series: | Medical Journal of Dr. D.Y. Patil Vidyapeeth |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/mjdrdypu.mjdrdypu_843_23 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846136028814901248 |
|---|---|
| author | Shalesh Rohatgi Pranit Khandait Satish Nirhale Prajwal Rao Pravin Naphade |
| author_facet | Shalesh Rohatgi Pranit Khandait Satish Nirhale Prajwal Rao Pravin Naphade |
| author_sort | Shalesh Rohatgi |
| collection | DOAJ |
| description | The incidence of hypomyelinating leukodystrophies is approximately 1 in every 250,000–500,000 individuals in the population. Hypomyelinating leukodystrophy-8 (HLD-8) is characterized by classical clinical features, including modest intellectual deficits and early-onset progressive cerebellar ataxia, with or without oligodontia and/or hypogonadotropic hypogonadism. In this case report, we present a 34-year-old male who experienced gradually progressive behavioral and memory disturbances over the past 10 years, accompanied by imbalance while walking and complex partial seizures. The patient also exhibited oligodontia and moderate intellectual disability (IQ score: 45). Spasticity was observed in the lower limbs, with exaggerated deep tendon reflexes in all four limbs, and bilaterally extensor plantar responses were noted. Sensory examination results were within normal limits. Bilateral cerebellar signs were present, including gaze-evoked nystagmus in all directions, which was non-fatigable. MRI brain revealed generalized cerebral and cerebellar atrophy, as well as diffuse hyperintensities in T2-weighted images (T2W) and fluid-attenuated inversion recovery (FLAIR) in the bilateral cerebral white matter, with no basal ganglia involvement. The sagittal T1-weighted image (T1W) showed diffuse thinning of the corpus callosum. Whole-exome sequencing revealed a novel variant mutation of the POLR3B gene in HLD-8, specifically in Exon 20 [c.2125A>G (p.Met709Val)] and Exon 23 [c.2699G>A (p.Arg900His)]. Very few case reports and variant mutations on the POLR3B gene on chromosome 12q23.3 have been reported thus far. |
| format | Article |
| id | doaj-art-86058e24036e4d47b5b529c688f6ebf8 |
| institution | Kabale University |
| issn | 2589-8302 2589-8310 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Medical Journal of Dr. D.Y. Patil Vidyapeeth |
| spelling | doaj-art-86058e24036e4d47b5b529c688f6ebf82024-12-09T09:31:30ZengWolters Kluwer Medknow PublicationsMedical Journal of Dr. D.Y. Patil Vidyapeeth2589-83022589-83102024-11-011761251125410.4103/mjdrdypu.mjdrdypu_843_23Novel Gene Mutation Variant in Hypomyelinating Leukodystrophy-8: A Case ReportShalesh RohatgiPranit KhandaitSatish NirhalePrajwal RaoPravin NaphadeThe incidence of hypomyelinating leukodystrophies is approximately 1 in every 250,000–500,000 individuals in the population. Hypomyelinating leukodystrophy-8 (HLD-8) is characterized by classical clinical features, including modest intellectual deficits and early-onset progressive cerebellar ataxia, with or without oligodontia and/or hypogonadotropic hypogonadism. In this case report, we present a 34-year-old male who experienced gradually progressive behavioral and memory disturbances over the past 10 years, accompanied by imbalance while walking and complex partial seizures. The patient also exhibited oligodontia and moderate intellectual disability (IQ score: 45). Spasticity was observed in the lower limbs, with exaggerated deep tendon reflexes in all four limbs, and bilaterally extensor plantar responses were noted. Sensory examination results were within normal limits. Bilateral cerebellar signs were present, including gaze-evoked nystagmus in all directions, which was non-fatigable. MRI brain revealed generalized cerebral and cerebellar atrophy, as well as diffuse hyperintensities in T2-weighted images (T2W) and fluid-attenuated inversion recovery (FLAIR) in the bilateral cerebral white matter, with no basal ganglia involvement. The sagittal T1-weighted image (T1W) showed diffuse thinning of the corpus callosum. Whole-exome sequencing revealed a novel variant mutation of the POLR3B gene in HLD-8, specifically in Exon 20 [c.2125A>G (p.Met709Val)] and Exon 23 [c.2699G>A (p.Arg900His)]. Very few case reports and variant mutations on the POLR3B gene on chromosome 12q23.3 have been reported thus far.https://journals.lww.com/10.4103/mjdrdypu.mjdrdypu_843_23hld-8hypomyelinating leukodystrophy-8novel variantpolr3b |
| spellingShingle | Shalesh Rohatgi Pranit Khandait Satish Nirhale Prajwal Rao Pravin Naphade Novel Gene Mutation Variant in Hypomyelinating Leukodystrophy-8: A Case Report Medical Journal of Dr. D.Y. Patil Vidyapeeth hld-8 hypomyelinating leukodystrophy-8 novel variant polr3b |
| title | Novel Gene Mutation Variant in Hypomyelinating Leukodystrophy-8: A Case Report |
| title_full | Novel Gene Mutation Variant in Hypomyelinating Leukodystrophy-8: A Case Report |
| title_fullStr | Novel Gene Mutation Variant in Hypomyelinating Leukodystrophy-8: A Case Report |
| title_full_unstemmed | Novel Gene Mutation Variant in Hypomyelinating Leukodystrophy-8: A Case Report |
| title_short | Novel Gene Mutation Variant in Hypomyelinating Leukodystrophy-8: A Case Report |
| title_sort | novel gene mutation variant in hypomyelinating leukodystrophy 8 a case report |
| topic | hld-8 hypomyelinating leukodystrophy-8 novel variant polr3b |
| url | https://journals.lww.com/10.4103/mjdrdypu.mjdrdypu_843_23 |
| work_keys_str_mv | AT shaleshrohatgi novelgenemutationvariantinhypomyelinatingleukodystrophy8acasereport AT pranitkhandait novelgenemutationvariantinhypomyelinatingleukodystrophy8acasereport AT satishnirhale novelgenemutationvariantinhypomyelinatingleukodystrophy8acasereport AT prajwalrao novelgenemutationvariantinhypomyelinatingleukodystrophy8acasereport AT pravinnaphade novelgenemutationvariantinhypomyelinatingleukodystrophy8acasereport |