Identification of Novel Mutations in the LRR-Cap Domain of<i>C21orf2</i>in Japanese Patients With Retinitis Pigmentosa and Cone–Rod Dystrophy

Suga, Akiko; Mizota, Atsushi; Kato, Mitsuhiro; Kuniyoshi, Kazuki; Yoshitake, Kazutoshi; Sultan, William; Yamazaki, Masashi; Shimomura, Yoshikazu; Ikeo, Kazuho; Tsunoda, Kazushige; Iwata, Takeshi

doi:10.1167/iovs.16-19450

Cited by 25 publications

(33 citation statements)

References 26 publications

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“…II:6 presented with severe CME beginning at age 39, but later also developed nyctalopia, mid-peripheral scotomas, and bone spicules ( Table 1 , Figure 2 and Figure 3 ). C21orf2 mutations have been reported in patients with early onset autosomal recessive RP and posterior staphyloma from Saudi Arabia [ 22 ], and patients with cone rod dystrophy and RP from Japan [ 23 ]. CME was not reported previously and prior reports documented more severe retinal degeneration than was observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Whole Genome Sequencing Revealed Mutations in Two Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi Jewish Pedigree

Gustafson

Duncan

Biswas

et al. 2017

Genes

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Retinitis pigmentosa (RP) causes progressive photoreceptor loss resulting from mutations in over 80 genes. This study identified the genetic cause of RP in three members of a non-consanguineous pedigree. Detailed ophthalmic evaluation was performed in the three affected family members. Whole exome sequencing (WES) and whole genome sequencing (WGS) were performed in the three affected and the two unaffected family members and variants were filtered to detect rare, potentially deleterious variants segregating with disease. WES and WGS did not identify potentially pathogenic variants shared by all three affected members. However, WES identified a previously reported homozygous nonsense mutation in KIZ (c.226C>T, p.Arg76*) in two affected sisters, but not in their affected second cousin. WGS revealed a novel 1.135 kb homozygous deletion in a retina transcript of C21orf2 and a novel 30.651 kb heterozygous deletion in CACNA2D4 in the affected second cousin. The sisters with the KIZ mutation carried no copies of the C21orf2 or CACNA2D4 deletions, while the second cousin with the C21orf2 and CACNA2D4 deletions carried no copies of the KIZ mutation. This study identified two independent, homozygous mutations in genes previously reported in autosomal recessive RP in a non-consanguineous family, and demonstrated the value of WGS when WES fails to identify likely disease-causing mutations.

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Section: Discussionmentioning

confidence: 99%

Whole Genome Sequencing Revealed Mutations in Two Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi Jewish Pedigree

Gustafson

Duncan

Biswas

et al. 2017

Genes

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“…Second, as a retrospective study, we did not precisely determine all possible anomalies in SIT. At the same time, some comorbidities that have been reported in SIT may be undetectable until youth or even adulthood, such as retinitis pigmentosa (Suga et al, ) and nephronophthisis (Stokman et al, ). Third, we acknowledge that a selection bias was possible, because SIT cases with associated conditions would be more likely to attend hospital and undergo systematic medical examination, which would generally be predicted to lead to a higher proportion of comorbidities in SIT.…”

Section: Discussionmentioning

confidence: 99%

Comorbidities in situs inversus totalis: A hospital‐based study

Chen

Guo

Qian

et al. 2020

Birth Defects Research

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Background and objective Few studies have assessed the comorbid diseases in situs inversus totalis (SIT) comprehensively. The aim of this study was to provide insight into the spectrum and prevalence of comorbidities in SIT. Methods Children ≤18 years of age with SIT were enrolled in this retrospective observational study. Situs status and comorbidities were independently confirmed by two physicians, based on review of radiologic, ultrasonic examination, operative records, and case notes. Results A total of 155 children (median age: 1.24 years; range: 1 day–17.8 years) confirmed to have SIT were recruited between January 2008 and December 2018. Associated conditions were diagnosed in 114 children (73.5%). Among them, 25 children (16.1%) had multiple anomalies affecting two or more organ systems. The most commonly associated conditions were congenital heart defects (n = 72, 46.5%) followed by primary ciliary dyskinesia (n = 19, 12.3%), renal disorders (n = 12, 7.7%), biliary atresia (n = 7, 4.5%), skeletal dysplasia (n = 8, 5.2%), and mental retardation (n = 4, 2.6%). Conclusion A substantial proportion of children with SIT have comorbidities affecting multiple systems, especially cardiovascular and respiratory abnormalities. Children with SIT warrant careful examination for the presence of congenital and acquired abnormalities.

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“…On the other hand, compound heterozygous CFAP410 variants (formed by c.319T>C (p.Y107H) and other variants) locating in both LRRCT and extra-LRRCT were previously identified in patients with SMDAX and RD 32 3. In addition, homozygous or compound heterozygous variants existing only in the LRRCT of CFAP410 were not previously reported in both sporadic ALS and SMDAX.…”

Section: Discussionmentioning

confidence: 98%

“…The variant of PXN was evaluated as a benign variant by SIFT, while the variant of CFAP410 was evaluated as probably damaging by both PolyPhen-2 and SIFT. This CFAP410 mutation is located in LRRCT (figure 1C), whose dysfunction causes reduced levels and affected localisations of CFAP410 protein products 3. In addition, CFAP410 interacts with NEK1, whose homozygous loss-of-function variants are implicated in up to 2% of patients with ALS.…”

Section: Discussionmentioning

confidence: 99%

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Retinitis pigmentosa prior to familial ALS caused by a homozygous cilia and flagella-associated protein 410 mutation

Kurashige

Morino

Matsuda

et al. 2019

J Neurol Neurosurg Psychiatry

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Identification of Novel Mutations in the LRR-Cap Domain ofC21orf2in Japanese Patients With Retinitis Pigmentosa and Cone–Rod Dystrophy

Cited by 25 publications

References 26 publications

Whole Genome Sequencing Revealed Mutations in Two Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi Jewish Pedigree

Whole Genome Sequencing Revealed Mutations in Two Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi Jewish Pedigree

Comorbidities in situs inversus totalis: A hospital‐based study

Retinitis pigmentosa prior to familial ALS caused by a homozygous cilia and flagella-associated protein 410 mutation

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