A Novel Variant in CWF19L1 Gene in a Family with Late-Onset Autosomal Recessive Cerebellar Ataxia 17

Algahtani, Hussein; Shirah, Bader; AlMatrafi, Samah A; Al-Qahtani, Mohammad H.; Abdulkareem, Angham Abdulrahman; Naseer, Muhammad Imran

doi:10.1080/01616412.2020.1831331

Cited by 7 publications

(16 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with the studies reporting that variants in CWF19L1 may cause ARCA, [8][9][10][11] we postulated that novel variants in CWF19L1 in our study may be related to ARCA in this family. However, neither such a variant has been reported in Chinese patients, nor has the same variant been previously described in the literature.…”

supporting

confidence: 93%

“…Consistent with these reports, morpholino‐mediated knockdown of CWF19L1 in zebrafish led to defective cerebellar structure and abnormal motor behavior. Recently, Algahtani et al 8 described a missense variant, c.395A > G, that changes Asp to Gly and is associated with a milder presentation of the phenotype. Although the existing findings cannot sufficiently explain the molecular mechanism of ARCA, they could be used as scientific evidence for the diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“… 1 , 2 , 3 , 4 , 5 Over the past two decades, more than 50 genes have been reported to cause ARCA, accounting for only 40% of cases. 6 , 7 One of these genes is CWF19L1 on chromosome 10q24, 8 which was recently identified and characterized to cause ARCA. 9 , 10 , 11 …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5] Over the past two decades, more than 50 genes have been reported to cause ARCA, accounting for only 40% of cases. 6,7 One of these genes is CWF19L1 on chromosome 10q24, 8 which was recently identified and characterized to cause ARCA. [9][10][11] The C19L1 protein encoded by the CWF19L1 gene contains 538 amino acids, including a metallophosphatase (MMP) domain, a histidine triad motif (HIT) domain, and a C-terminal Cwf-J-C domain 12,13 (Figure 1).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Heterozygous pathogenic variants in CWF19L1 in a Chinese family with spinocerebellar ataxia, autosomal recessive 17

Ruan

Wang

Zhu

et al. 2022

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Autosomal recessive cerebellar ataxia (ARCA) is a rare neurological disorder that affects both the peripheral and central nervous systems and occurs primarily in children. [1][2][3] The incidence of ARCA has been reported to be 0-7.2 per 100,000 children. 4 Previous studies have described that patients have varied clinical manifestations, ranging from progressive cerebellar syndromes, as a key feature, to

show abstract

supporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Heterozygous pathogenic variants in CWF19L1 in a Chinese family with spinocerebellar ataxia, autosomal recessive 17

Ruan

Wang

Zhu

et al. 2022

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

“…In this study, we identified a novel homozygous missense mutation ERCC8:c176T>C (p.M59T) segregating with cerebellar ataxia in a consanguineous Pakistani family. We used WES, which has previously identified novel genes involved in rare neurological disorders including ataxia, especially in the setting of consanguinity [21]. Mutations in ERCC8 have been associated with defects in the transcription-coupled nucleotide excision repair (TC-NER) leading to CSA [22], characterized mainly by growth failure, microcephaly and developmental delay [23].…”

Section: Discussionmentioning

confidence: 99%

A Novel Missense Mutation in ERCC8 Co-Segregates with Cerebellar Ataxia in a Consanguineous Pakistani Family

Gauhar

Tejwani

Abdullah

et al. 2022

Cells

View full text Add to dashboard Cite

Autosomal-recessive cerebellar ataxias (ARCAs) are heterogeneous rare disorders mainly affecting the cerebellum and manifest as movement disorders in children and young adults. To date, ARCA causing mutations have been identified in nearly 100 genes; however, they account for less than 50% of all cases. We studied a multiplex, consanguineous Pakistani family presenting with a slowly progressive gait ataxia, body imbalance, and dysarthria. Cerebellar atrophy was identified by magnetic resonance imaging of brain. Using whole exome sequencing, a novel homozygous missense mutation ERCC8:c.176T>C (p.M59T) was identified that co-segregated with the disease. Previous studies have identified homozygous mutations in ERCC8 as causal for Cockayne Syndrome type A (CSA), a UV light-sensitive syndrome, and several ARCAs. ERCC8 plays critical roles in the nucleotide excision repair complex. The p.M59T, a substitution mutation, is located in a highly conserved WD1 beta-transducin repeat motif. In silico modeling showed that the structure of this protein is significantly affected by the p.M59T mutation, likely impairing complex formation and protein-protein interactions. In cultured cells, the p.M59T mutation significantly lowered protein stability compared to wildtype ERCC8 protein. These findings expand the role of ERCC8 mutations in ARCAs and indicate that ERCC8-related mutations should be considered in the differential diagnosis of ARCAs.

show abstract

Autosomal recessive adult onset ataxia

et al. 2021

View full text Add to dashboard Cite

A Novel Variant in CWF19L1 Gene in a Family with Late-Onset Autosomal Recessive Cerebellar Ataxia 17

Cited by 7 publications

References 10 publications

Heterozygous pathogenic variants in CWF19L1 in a Chinese family with spinocerebellar ataxia, autosomal recessive 17

Heterozygous pathogenic variants in CWF19L1 in a Chinese family with spinocerebellar ataxia, autosomal recessive 17

A Novel Missense Mutation in ERCC8 Co-Segregates with Cerebellar Ataxia in a Consanguineous Pakistani Family

Autosomal recessive adult onset ataxia

Contact Info

Product

Resources

About