Clinical features of collagen VI-related dystrophies: A large Brazilian cohort

Zanoteli, Edmar; Soares, Priscilla Souza; Silva, André Macedo Serafim; Camelo, Clara Gontijo; Fonseca, Alulin Tácio Quadros Santos Monteiro; Albuquerque, Marco Antônio Veloso; Moreno, Cristiane Araújo Martins; Neto, Osorio Lopes Abath; Filho, Gil Monteiro Novo; Kulikowski, Leslie Domenici; Reed, Umbertina Conti

doi:10.1016/j.clineuro.2020.105734

Cited by 9 publications

(12 citation statements)

References 29 publications

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“…From the genetic information, we have established the mutation pro le of the largest cohort at a single center as far as we are aware. The majority of the variants were mono-allelic (86%, 120/140), and 67% (94/140) of them were likely to be de novo because the parents of the patients were not affected, as has previously been described [6,9,10,17,18]. Therefore, our mutation pro le may be useful as a reference for diverse ethnicities.…”

Section: Resultsmentioning

confidence: 56%

“…Mono-allelic variants in the THD must be primarily associated with the majority SSCD staining pattern (91%, 92/101) and UCMD phenotype (90%, 94/105), whilst mono-allelic variants outside the THD were also associated with SSCD (71%, 10/14) but a BM phenotype (93%, 14/15). In exceptional cases, genotypes cannot be associated with speci c phenotypes, with some variants reported to cause both UCMD and BM phenotypes [9][10][11]18]. In fact, in our cohort, the families with c.877G>A in COL6A1, c.856-2A>G in COL6A2, or c.943G>A in COL6A2 showed a wide range of phenotypes from milder BM to severer UCMD, while conversely the variation in phenotypes of families with c.956A>G or c.1022G>A in COL6A1 was quite narrow and on the border between UCMD and BM.…”

Section: Resultsmentioning

confidence: 99%

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Mutation Profile of Collagen VI-Related Myopathy in Japan

Inoue

Saito

Yonekawa

et al. 2021

Preprint

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Background: Collagen VI-related myopathy spans a clinical continuum from severe Ullrich congenital muscular dystrophy to milder Bethlem myopathy. This disease is caused by mutations in COL6A1, COL6A2, or COL6A3. Most reported mutations are de novo; therefore, to identify possible associated mutations, comprehensive large cohort studies are required for different ethnicities.Methods: We retrospectively reviewed clinical information, muscle histology, and genetic analyses from 147 Japanese patients representing 130 families, whose samples were sent for diagnosis to the National Center of Neurology and Psychiatry between July 1979 and January 2020. Genetic analyses were conducted by gene-based resequencing, targeted panel resequencing, and whole exome sequencing, in combination with cDNA analysis.Results: Of a total of 130 families with 1-5 members with collagen VI-related myopathy, 120 had mono-allelic and 10 had bi-allelic variants of COL6A1, COL6A2, or COL6A3. Among them, 60 variants were in COL6A1, 57 in COL6A2, and 23 in COL6A3, including 37 novel variants. Mono-allelic variants were classified into four groups: missense (69, 58%), splicing (40, 33%), small in-frame deletion (7, 6%), and large genomic deletion (4, 3%). Variants in the triple helical domains accounted for 88% (105/120) of all mono-allelic variants. Conclusions: We report the mutation profile of a large set of Japanese cases of collagen VI-related myopathy. This dataset can be used as a reference to support genetic diagnosis and mutation-specific treatment.

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Section: Resultsmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Mutation Profile of Collagen VI-Related Myopathy in Japan

Inoue

Saito

Yonekawa

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…From the genetic information, we have established the causative variant profile of the largest cohort at a single center as far as we are aware. The majority of the variants were mono-allelic (86%, 120/140), and 67% (94/140) of them were likely to be de novo because the parents of the patients were not apparently affected and their DNAs were not available, as has previously been described [ 11 , 14 , 15 , 22 – 24 ]. Therefore, our causative variant profile may be useful as a reference for diverse ethnicities.…”

Section: Discussionmentioning

confidence: 98%

“…In contrast, mono-allelic variants outside the THD were also associated with SSCD (71%, 10/14) but a BM phenotype (93%, 14/15) (Table 2 ). However, as shown in the literatures, genotypes cannot be associated with specific phenotypes, with some variants reported to cause both UCMD and BM phenotypes [ 14 – 16 , 24 ]. In fact, in our cohort, the families with c.877G>A in COL6A1 , c.856-2A>G in COL6A2 , or c.943G>A in COL6A2 showed a wide range of phenotypes from milder BM to severer UCMD, while conversely the variation in phenotypes of families with c.956A>G or c.1022G>A in COL6A1 was quite narrow and those families showed BM or intermediate phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Causative variant profile of collagen VI-related dystrophy in Japan

Inoue

Ohsawa

Yonekawa

et al. 2021

Orphanet J Rare Dis

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Background Collagen VI-related dystrophy spans a clinical continuum from severe Ullrich congenital muscular dystrophy to milder Bethlem myopathy. This disease is caused by causative variants in COL6A1, COL6A2, or COL6A3. Most reported causative variants are de novo; therefore, to identify possible associated causative variants, comprehensive large cohort studies are required for different ethnicities. Methods We retrospectively reviewed clinical information, muscle histology, and genetic analyses from 147 Japanese patients representing 130 families, whose samples were sent for diagnosis to the National Center of Neurology and Psychiatry between July 1979 and January 2020. Genetic analyses were conducted by gene-based resequencing, targeted panel resequencing, and whole exome sequencing, in combination with cDNA analysis. Results Of a total of 130 families with 1–5 members with collagen VI-related dystrophy, 120 had mono-allelic and 10 had bi-allelic variants in COL6A1, COL6A2, or COL6A3. Among them, 60 variants were in COL6A1, 57 in COL6A2, and 23 in COL6A3, including 37 novel variants. Mono-allelic variants were classified into four groups: missense (69, 58%), splicing (40, 33%), small in-frame deletion (7, 6%), and large genomic deletion (4, 3%). Variants in the triple helical domains accounted for 88% (105/120) of all mono-allelic variants. Conclusions We report the causative variant profile of a large set of Japanese cases of collagen VI-related dystrophy. This dataset can be used as a reference to support genetic diagnosis and variant-specific treatment.

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“…[ 15 ] In cohort studies conducted to date, hypertension has not been reported in patients with COL6-related myopathy. [ 2 16 ] van der Kooi and colleagues did not find any cardiac abnormality in a Dutch family with COL6A2 mutation. [ 17 ] Only, Bao and colleagues reported a patient with recurrent hematuria, and after whole-exome sequencing analysis, they speculated that impaired interaction between COL6 and COL4 results in haematuria.…”

Section: Discussionmentioning

confidence: 99%

Genotype-Phenotype Correlation of the Childhood-Onset Bethlem Myopathy in the Mediterranean Region of Turkey

Kutluk

Kadem

Bektaş

et al. 2021

Annals of Indian Academy of Neurology

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Objectives: Collagen-VI-related myopathies are caused by both dominant and recessive mutations in the three collagen-VI-related genes (COL6A1, COL6A2, and COL6A3) and present as two different major clinical entities; Bethlem myopathy and Ullrich congenital muscular dystrophy. Methods: In this study, we evaluated the clinical, pathologic, and genetic features of 8 patients with Bethlem myopathy from 3 families. Results: We inspected disease course differences with age and mutations. Different variants in COL6A1 and COL6A2 genes were detected. Muscle MRI of the lower limbs showed a specific pattern of muscle involvement with variable severity of fatty infiltration. One family had essential hypertension. Conclusion: Genotype-phenotype correlation studies are critical in determining gene or mutation-targeted therapies, patient follow-up, severity and progression prediction, and genetic counselling.

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Clinical features of collagen VI-related dystrophies: A large Brazilian cohort

Cited by 9 publications

References 29 publications

Mutation Profile of Collagen VI-Related Myopathy in Japan

Mutation Profile of Collagen VI-Related Myopathy in Japan

Causative variant profile of collagen VI-related dystrophy in Japan

Genotype-Phenotype Correlation of the Childhood-Onset Bethlem Myopathy in the Mediterranean Region of Turkey

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