Clinical, histological, and genetic characterization of PYROXD1-related myopathy

Lornage, Xavière; Schartner, Vanessa; Balbueno, Inès; Biancalana, Valérie; Willis, Tracey; Echaniz‐Laguna, Andoni; Scheidecker, Sophie; Quinlivan, R.; Fardeau, Michel; Malfatti, Edoardo; Lannes, Béatrice; Sewry, Caroline A.; Romero, Norma B.; Laporte, Jocelyn; Böhm, Johann

doi:10.1186/s40478-019-0781-8

Cited by 18 publications

(34 citation statements)

References 12 publications

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“…Pulmonary function tests in Patient II‐1 demonstrated a mild obstructive and possible restrictive pattern as well as decreased diffusion capacity. This finding is consistent with other reports of a restrictive pattern of pulmonary function in other cases of PYROXD1 ‐associated myopathy . Lornage et al .…”

Section: Discussionsupporting

confidence: 93%

“…described one patient with possible cardiomyopathy and Lornage et al . described one patient with mild septal and anteroseptal dyskinesia . However, the majority of patients with PYROXD1 ‐associated myopathy (including the patients reported in this paper) did not show signs of cardiomyopathy even at advanced age .…”

Section: Discussionmentioning

confidence: 56%

“…originally reported facial weakness, nasal speech and hyporeflexivity as universal features in the first nine patients with PYROXD1 ‐related autosomal recessive myopathy . However, these features have not been consistently reported in other patients with PYROXD1 ‐associated myopathy …”

Section: Discussionmentioning

confidence: 99%

“…Myopathy associated with PYROXD1 pathogenic variants was initially described with an onset in infancy or childhood, although adult‐onset myopathy has also been reported (Table S1). Cardiomyopathy and restrictive lung disease have also been reported in PYROXD1 ‐associated myopathy, although these phenotypes are variable …”

Section: Introductionmentioning

confidence: 99%

“…In the previously reported and unrelated families affected by myopathy, both compound heterozygous and homozygous variants in PYROXD1 including loss‐of‐function variants were reported. Causal variants identified to date include splice‐site mutations (c.285+1G>A and c.414+1G>A), missense variants (p.Asn155Ser, p.Tyr354 and p.Gly372His), frameshift variants (c.1159_1160insCAAA, p.Ala387fs*13) and a deep intronic variant (c.415‐976A>G) . The c.464A>G single nucleotide variant that is predicted to result in a nonsynonymous change p.Asn155Ser is observed in multiple independent families.…”

Section: Introductionmentioning

confidence: 99%

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Myopathy associated with homozygous PYROXD1 pathogenic variants detected by genome sequencing

et al. 2020

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Biallelic pathogenic variants in the gene PYROXD1 have recently been described to cause early‐onset autosomal recessive myopathy. Myopathy associated with PYROXD1 pathogenic variants is rare and reported in only 17 individuals. Known pathogenic variants in PYROXD1 include missense, insertion and essential splice‐site variants. Here we describe a consanguineous family of individuals affected with late‐onset myopathy and homozygous PYROXD1 missense variants (NM_024854.5:c.464A>G [p.Asn155Ser]) expanding our understanding of the possible disease phenotypes of PYROXD1‐associated myopathy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Myopathy associated with homozygous PYROXD1 pathogenic variants detected by genome sequencing

et al. 2020

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Genetics of the Congenital Myopathies

Pelin¹

2021

Encyclopedia of Life Sciences

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The congenital myopathies are a heterogeneous group of skeletal muscle disorders characterised by muscle weakness present at birth and typical abnormalities in skeletal muscle fibres, such as protein aggregates, centrally located nuclei or areas lacking mitochondria. Mutations in more than 30 different genes can cause a congenital myopathy. The inheritance can be autosomal dominant, autosomal recessive or X‐linked or sporadic due to novel mutations. The mutated genes can be divided into three groups: genes encoding proteins of the skeletal muscle sarcomere, genes encoding proteins of the sarcoplasmic reticulum and transverse tubules and genes encoding proteins regulating muscle growth and regeneration. The mutations cause impaired or reduced muscle contraction by damaging the contractile machinery or by altering the regulation of muscle contraction, leading to muscle weakness. There is considerable clinical and histological overlap between the different types of congenital myopathies. The inheritance can be autosomal dominant, autosomal recessive or X‐linked or sporadic ( de novo mutations). Disease‐causing variants in more than 30 different genes can cause a congenital myopathy. Disease‐causing variants in the same gene can result in more than one clinical phenotype, and the same clinical phenotype can result from mutations in several different genes. The genes encode proteins essential for skeletal muscle development, muscle contraction, structure and protein turnover.

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Clinical and genetic characterization of PYROXD1‐related myopathy patients from Turkey

Daimagüler

Akpulat

Özdemir

et al. 2021

American J of Med Genetics Pt A

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Congenital myopathies (CMs) are a heterogeneous group of inherited muscle disorders characterized by muscle weakness at birth, while limb‐girdle muscular dystrophies (LGMD) have a later onset and slower disease progression. Thus, detailed clinical phenotyping of genetically defined disease entities are required for the full understanding of genotype–phenotype correlations. A recently defined myopathic genetic disease entity is caused by bi‐allelic variants in a gene coding for pyridine nucleotide‐disulfide oxidoreductase domain 1 (PYROXD1) with unknown substrates. Here, we present three patients from two consanguineous Turkish families with mild LGMD, facial weakness, normal CK levels, and slow progress. Genomic analyses revealed a homozygous known pathogenic missense variant (c.464A>G, p.Asn155Ser) in family 1 with two affected females. In the affected male of family 2, we found this variant in a compound heterozygous state together with a novel frameshift variant (c.329_332delTCTG, p.Leu112Valfs*8), which is the second frameshift variant known so far in PYROXD1. We have been able to define a large homozygous region in family 1 sharing a common haplotype with family 2 in the critical region. Our data suggest that c.464A>G is a Turkish founder mutation. To gain deeper insights, we performed a systematic review of all published PYROXD1‐related myopathy cases. Our analysis showed that the c.464A > G variant was found in 87% (20/23) of the patients and that it may cause either a childhood‐ or adult‐onset phenotype, irrespective of its presence in a homozygous or compound heterozygous state. Interestingly, only four patients had elevated CK levels (up to 1000 U/L), and cardiac involvement was found in few compound heterozygous cases.

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Clinical, histological, and genetic characterization of PYROXD1-related myopathy

Cited by 18 publications

References 12 publications

Myopathy associated with homozygous PYROXD1 pathogenic variants detected by genome sequencing

Myopathy associated with homozygous PYROXD1 pathogenic variants detected by genome sequencing

Genetics of the Congenital Myopathies

Clinical and genetic characterization of PYROXD1‐related myopathy patients from Turkey

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