Phenotype of heterozygous variants of dehydrodolichol diphosphate synthase.
Adolescent
Alkyl and Aryl Transferases
/ genetics
Brain
/ physiopathology
Child
Child, Preschool
Electroencephalography
Epilepsies, Myoclonic
/ genetics
Evoked Potentials, Somatosensory
/ genetics
Female
Genotype
Humans
Male
Phenotype
Seizures
/ genetics
Status Epilepticus
/ genetics
Tremor
/ genetics
Exome Sequencing
Journal
Developmental medicine and child neurology
ISSN: 1469-8749
Titre abrégé: Dev Med Child Neurol
Pays: England
ID NLM: 0006761
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
accepted:
02
06
2021
pubmed:
19
7
2021
medline:
28
12
2021
entrez:
18
7
2021
Statut:
ppublish
Résumé
To further identify and broaden the phenotypic characteristics and genotype spectrum of the dehydrodolichol diphosphate synthase (DHDDS) gene. Pathogenic variants of DHDDS were identified by whole-exome sequencing; clinical data of 10 patients (six males, four females; age range 2-14y; mean age 5y 9mo, SD 3y 3mo) were collected and analysed. All patients had seizures, and myoclonic seizures could be seen in eight patients, with myoclonic status epilepticus in three. The interictal electroencephalogram (EEG) in four patients at seizure onset showed generalized slow waves, slow wave mixed spikes, and spike and waves. Tremor, ataxia, and hypertonia was observed in six, five, and three patients respectively. The results of short-latency somatosensory evoked potential in two patients were normal, and the symptom of tremor was captured on EEG without time-locked discharges in one patient, suggesting that the tremor in both patients was a motor impairment rather than myoclonic seizures. Global developmental delay occurred in all patients, among whom nine showed severe intellectual disability and one moderate. Five DHDDS variants were identified, three of which have not been reported previously. Myoclonic seizure is the most common seizure type in heterozygous DHDDS variants, while myoclonic status epilepticus can also occur. The pattern of interictal EEG discharges is characterized by slow waves rather than spike and waves, and generalized discharges was prominent.
Substances chimiques
Alkyl and Aryl Transferases
EC 2.5.-
dehydrodolichyl diphosphate synthetase
EC 2.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
125-134Informations de copyright
© 2021 Mac Keith Press.
Références
DeRamus ML, Davis SJ, Rao SR, et al. Selective ablation of dehydrodolichyl diphosphate synthase in murine retinal pigment epithelium (RPE) causes RPE atrophy and retinal degeneration. Cells 2020; 9: 771.
Fujihashi M, Zhang YW, Higuchi Y, Li XY, Koyama T, Miki K. Crystal structure of cis-prenyl chain elongating enzyme, undecaprenyl diphosphate synthase. Proc Natl Acad Sci USA 2001; 98: 4337-422.
Grabińska KA, Park EJ, Sessa WC. cis-Prenyltransferase: new insights into protein glycosylation, rubber synthesis, and human diseases. J Biol Chem 2016; 291: 18582-90.
Hamdan FF, Myers CT, Cossette P, et al. High rate of recurrent de novo mutations in developmental and epileptic encephalopathies. Am J Hum Genet 2017; 101: 664-85.
Park EJ, Grabińska KA, Guan Z, et al. Mutation of Nogo-B receptor, a subunit of cis-prenyltransferase, causes a congenital disorder of glycosylation. Cell Metab 2014; 20: 448-57.
Sabry S, Vuillaumier-Barrot S, Mintet E, et al. A case of fatal type I congenital disorders of glycosylation (CDG I) associated with low dehydrodolichol diphosphate synthase (DHDDS) activity. Orphanet J Rare Dis 2016; 11: 84.
Zelinger L, Banin E, Obolensky A, et al. A missense mutation in DHDDS, encoding dehydrodolichyl diphosphate synthase, is associated with autosomal-recessive retinitis pigmentosa in Ashkenazi Jews. Am J Hum Genet 2011; 88: 207-15.
Biswas P, Duncan JL, Maranhao B, et al. Genetic analysis of 10 pedigrees with inherited retinal degeneration by exome sequencing and phenotype-genotype association. Physiol Genomics 2017; 49: 216-29.
Kimchi A, Khateb S, Wen R, et al. Nonsyndromic retinitis pigmentosa in the Ashkenazi Jewish population: genetic and clinical aspects. Ophthalmology 2018; 125: 725-34.
Togashi N, Fujita A, Shibuya M, et al. Fifteen-year follow-up of a patient with a DHDDS variant with non-progressive early onset myoclonic tremor and rare generalized epilepsy. Brain Dev 2020; 42: 696-9.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17: 405-24.
Edani BH, Grabińska KA, Zhang R, et al. Structural elucidation of the cis-prenyltransferase NgBR/DHDDS complex reveals insights in regulation of protein glycosylation. Proc Natl Acad Sci USA 2020; 117: 20794-802.
Bar-El ML, Vaňková P, Yeheskel A, et al. Structural basis of heterotetrameric assembly and disease mutations in the human cis-prenyltransferase complex. Nat Commun 2020; 11: 5273.
Takahashi S, Koyama T. Structure and function of cis-prenyl chain elongating enzymes. Chem Rec 2006; 6: 194-205.