Whole‐exome sequencing for variant discovery in blepharospasm

Tian, Jun; Vemula, Satya R.; Xiao, Jianfeng; Valente, Enza Maria; Defazio, Giovanni; Petrucci, Simona; Gigante, Angelo Fabio; Rudzińska‐Bar, Monika; Wszołek, Zbigniew K.; Kennelly, Kathleen D.; Uitti, Ryan J.; Gerpen, Jay A. van; Hedera, Peter; Trimble, Elizabeth J.; LeDoux, Mark S.

doi:10.1002/mgg3.411

Cited by 22 publications

(18 citation statements)

References 98 publications

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“…Deleterious mutations in HS1BP3 encoding hematopoietic cell-specific Lyn substrate 1-binding protein 3 (NM_022460.3: c.94C>A, p.Gly32Cys) and GNA14 encoding G protein subunit α14 (NM_004297.3: c.989_990del, p.Thr330ArgfsTer67) were present in a father and son with segmental CCD that initially presented as BSP. Additionally, deleterious variants of genes encoding dynein axonemal heavy chain ( DNAH17 ); transient receptor potential cation channel subfamily V member 4 ( TRPV4 ); calpain 11 ( CAPN11 ); vacuolar protein sorting 13 homolog C ( VPS13C ); unc-13 homolog B ( UNC13B ); spectrin β, non-erythrocytic 4 ( SPTBN4 ); myogenic differentiation 1 ( MYOD1 ); and mitochondrial ribosomal protein L15 ( MRPL15 ) have been found in two or more unrelated BSP patients ( 78 ). Despite the identification of many gene mutations in BSP, OMD, and MS patients, the mutation rates of these genes are low and it is a lack of functional experiments of mutant genes.…”

Section: Geneticsmentioning

confidence: 99%

Blepharospasm, Oromandibular Dystonia, and Meige Syndrome: Clinical and Genetic Update

Liang-jun

et al. 2021

Front. Neurol.

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Meige syndrome (MS) is cranial dystonia characterized by the combination of upper and lower cranial involvement and including binocular eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). The etiology and pathogenesis of this disorder of the extrapyramidal system are not well-understood. Neurologic and ophthalmic examinations often reveal no abnormalities, making diagnosis difficult and often resulting in misdiagnosis. A small proportion of patients have a family history of the disease, but to date no causative genes have been identified to date and no cure is available, although botulinum toxin A therapy effectively mitigates the symptoms and deep brain stimulation is gaining increasing attention as a viable alternative treatment option. Here we review the history and progress of research on MS, BSP, and OMD, as well as the etiology, pathology, diagnosis, and treatment.

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Section: Geneticsmentioning

confidence: 99%

Blepharospasm, Oromandibular Dystonia, and Meige Syndrome: Clinical and Genetic Update

Liang-jun

et al. 2021

Front. Neurol.

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“…Therefore, in this study we examined 151 genes in all BEB patients and found SYNE1 gene mutation in seven cases, CIZ1 gene mutation in two cases, CACNA1A gene mutation in two cases, LRRK2 gene mutation in two cases, FUS gene mutation in two cases, and C10orf2, TPP1, SLC1A3, PNKD, EIF4G1, SETX, PRRT2, SPTBN2, and TTBK2 gene mutation in each case. Interestingly, a recent study showed that deleterious variants in CACNA1A, REEP4, TOR2A, ATP2A3, HS1BP3, GNA14, and DNAH17 were involved in blepharospasm, and none of these variants except for CACNA1A has been reported to be associated with blepharospasm (15). However, a follow-up study reported that all variants detected in GNAL, CIZ1, and TOR2A seemed to be benign in 132 blepharospasm patients (16).…”

Section: Discussionmentioning

confidence: 99%

Screening Gene Mutations in Chinese Patients With Benign Essential Blepharospasm

et al. 2020

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This study aimed to screen gene mutations in Chinese patients with benign essential blepharospasm (BEB) to understand its etiology. Methods: Twenty BEB patients diagnosed by clinical manifestations between April 2015 and October 2015 were enrolled. All the cases were investigated by questionnaires about general conditions, social behavioral factors, environmental factors, psychological factors, genetic factors, and previous diseases. In each patient, a total of 151 genes related to movement disorders were analyzed by second-generation sequencing. Results: Two patients had a family history of BEB, and they had SYNE1 and Cdkn1A-interacting zinc finger protein 1 (CIZ1) mutation, respectively. We found the SYNE1 mutation in seven patients, the CIZ1 mutation in two patients, the CACNA1A mutation in two patients, the LRRK2 mutation in two patients, and the FUS mutation in two patients. The C10orf2, TPP1, SLC1A3, PNKD, EIF4G1, SETX, PRRT2, SPTBN2, and TTBK2 mutations were found in only one patient, respectively, while not any mutation in the 151 genes were found in two patients. Some patients had mutations in two genes. Conclusion: Genetic factors, especially SYNE1 and CIZ1 mutations, contribute to the etiology of BEB.

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“…The second stage of genetic analysis was performed with whole exome sequencing (WES) of three subjects (II/2, III/1, and III/2) using Illumina HiSeq 2500 platform (Illumina, San Diego, CA, USA). Genomic DNA was sheared to yield 100–450 base pair (bp) fragments, which was described before [ 16 ]. In-solution whole-exome capture and massively parallel sequencing was performed using the Agilent SureSelect XT All Exon Kit 51 Mb (Agilent, Santa Clara, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Novel Type of Complicated Autosomal Dominant Hereditary Spastic Paraplegia Associated with Congenital Distal Arthrogryposis Type I

et al. 2018

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Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurological disorders. HSP is classified as pure when only a spastic weakness of the lower extremities is present. Complex HSP comes with additional neurological or systemic abnormalities. Complex HSP with skeletal abnormalities is rare and mostly seen in autosomal recessive HSP. Autosomal dominant (AD) complex HSP with skeletal abnormalities are consistently seen only in SPG9 (spastic gait type 9). In this paper, we report a kindred condition with AD HSP among four living affected individuals who had progressive, adult onset spastic paraparesis that was associated with a distal arthrogryposis (DA) in every affected individual. They also had episodes of rhabdomyolysis without any clinical signs of myopathy. Exhaustive genetic analysis including targeted sequencing of known HSP and DA genes and whole exome sequencing did not identify the disease-causing gene. It excluded all known HSP and DA genes. We propose that this is a novel genetic type of complex AD HSP. Elucidation of a genetic cause of this type of HSP will further contribute to our understanding of axonal degeneration and skeletal abnormalities.

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Whole‐exome sequencing for variant discovery in blepharospasm

Cited by 22 publications

References 98 publications

Blepharospasm, Oromandibular Dystonia, and Meige Syndrome: Clinical and Genetic Update

Blepharospasm, Oromandibular Dystonia, and Meige Syndrome: Clinical and Genetic Update

Screening Gene Mutations in Chinese Patients With Benign Essential Blepharospasm

Novel Type of Complicated Autosomal Dominant Hereditary Spastic Paraplegia Associated with Congenital Distal Arthrogryposis Type I

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