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| Distal myopathies v7.4 | DYSF |
Achchuthan Shanmugasundram changed review comment from: PMID:17287450 (2007) reported two unrelated patuients, one with limb girdle weakness and the other with distal weakness, who presented with elecvated CK, patholgical MRI and reduced dysferlin expression in a muscle biopsy specimen. First patient was the sister of an autosomal recessive limb-girdle muscular dystrophy patient and patient 2 was the father of two offspring with Miyoshi myopathy. The two patients wer identified with variant in one allele (patient 1: p.Asp625Tyr; patient 2: p.Gly519Arg) of DYSF gene, whereas as family members with AR disease harboured compund heterozygous or homozygous variants. PMID:21658164 (2011) reported two unrelated patients identified with a heterozygous variant in DYSF gene (p.Glu1763Asp). First patient had proximal weakness of the lower limbs and was unable to walk on her toes and heels since the age of 18 years and her brother had asymptomatic hyperCKemia. Second pateint, who was previolusly active in sports presented in late adolescence with distal myopathy. Both patients had high CK activity and electromyography showed myopathic changes. The parents of neither patients had muscle weakness. The variant was found in heterozygous state in mother, grandfather and brother of patient 1, while it is not detected in father of patient 2 and mother's DNA wasn't available. PMID:29879922 (2018) reported a South African family of mixed descent in which all affetced first generation (G1) members presented with a predominant distal ‘posterior calf’ myopathy starting in early adulthood. Their offspring (G2) experienced severe unexpected symptoms of myalgia and cramps since adolescence. All affected G1 individuals were homozygous for a novel truncating p.Tyr1433Ter DYSF variant, with their asymptomatic sibling and pauci-symptomatic G2 offspring carrying only a single variant allele. PMID:35962550 (2022) reported a large family with progressive muscular dystrophy and hyperCKaemia and was identified with a monoallelic novel DYSF variant (p.Tyr2070Metfs*4). Skeletal muscle involvement was milder and later onset than typical dysferlinopathy presentations; these clinical signs manifested in four individuals, all between the fourth and sixth decades of life. The study showed a consistent dysferlinopathy phenotype across three generations, with dystrophic muscle changes and fatty replacement, reduced dysferlin protein expression, but no evidence that the C‑terminal DYSF variant triggers mRNA decay. Monoallelic DYSF variants are not yet associated with any phenotypes in OMIM.; to: PMID:17287450 (2007) reported two unrelated patuients, one with limb girdle weakness and the other with distal weakness, who presented with elecvated CK, patholgical MRI and reduced dysferlin expression in a muscle biopsy specimen. First patient was the sister of an autosomal recessive limb-girdle muscular dystrophy patient and patient 2 was the father of two offspring with Miyoshi myopathy. The two patients wer identified with variant in one allele (patient 1: p.Asp625Tyr; patient 2: p.Gly519Arg) of DYSF gene, whereas as family members with AR disease harboured compund heterozygous or homozygous variants. PMID:21658164 (2011) reported two unrelated patients identified with a heterozygous variant in DYSF gene (p.Glu1763Asp). First patient had proximal weakness of the lower limbs and was unable to walk on her toes and heels since the age of 18 years and her brother had asymptomatic hyperCKemia. Second patient, who was previously active in sports presented in late adolescence with distal myopathy. Both patients had high CK activity and electromyography showed myopathic changes. The parents of neither patients had muscle weakness. The variant was found in heterozygous state in mother, grandfather and brother of patient 1, while it is not detected in father of patient 2 and mother's DNA wasn't available. PMID:29879922 (2018) reported a South African family of mixed descent in which all affetced first generation (G1) members presented with a predominant distal ‘posterior calf’ myopathy starting in early adulthood. Their offspring (G2) experienced severe unexpected symptoms of myalgia and cramps since adolescence. All affected G1 individuals were homozygous for a novel truncating p.Tyr1433Ter DYSF variant, with their asymptomatic sibling and pauci-symptomatic G2 offspring carrying only a single variant allele. PMID:35962550 (2022) reported a large family with progressive muscular dystrophy and hyperCKaemia and was identified with a monoallelic novel DYSF variant (p.Tyr2070Metfs*4). Skeletal muscle involvement was milder and later onset than typical dysferlinopathy presentations; these clinical signs manifested in four individuals, all between the fourth and sixth decades of life. The study showed a consistent dysferlinopathy phenotype across three generations, with dystrophic muscle changes and fatty replacement, reduced dysferlin protein expression, but no evidence that the C‑terminal DYSF variant triggers mRNA decay. Monoallelic DYSF variants are not yet associated with any phenotypes in OMIM. |
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| Distal myopathies v7.4 | DYSF |
Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are at least 6 unrelated families with heterozygous carrier individuals presenting with a limb-girdle muscular dystrophy/ distal myopathy phenotype despite it being milder and later-onset than individuals with biallelic variants. There is also evidence of some heterozygous carriers from two of the families not displaying phenotype suggesting reduced penetrance. As there are six unrelated families with monoalellic phenotype, the MOI should be updated to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' in the next GMS update. |
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| Distal myopathies v7.2 | DYSF |
Achchuthan Shanmugasundram edited their review of gene: DYSF: Added comment: PMID:17287450 (2007) reported two unrelated patuients, one with limb girdle weakness and the other with distal weakness, who presented with elecvated CK, patholgical MRI and reduced dysferlin expression in a muscle biopsy specimen. First patient was the sister of an autosomal recessive limb-girdle muscular dystrophy patient and patient 2 was the father of two offspring with Miyoshi myopathy. The two patients wer identified with variant in one allele (patient 1: p.Asp625Tyr; patient 2: p.Gly519Arg) of DYSF gene, whereas as family members with AR disease harboured compund heterozygous or homozygous variants. PMID:21658164 (2011) reported two unrelated patients identified with a heterozygous variant in DYSF gene (p.Glu1763Asp). First patient had proximal weakness of the lower limbs and was unable to walk on her toes and heels since the age of 18 years and her brother had asymptomatic hyperCKemia. Second pateint, who was previolusly active in sports presented in late adolescence with distal myopathy. Both patients had high CK activity and electromyography showed myopathic changes. The parents of neither patients had muscle weakness. The variant was found in heterozygous state in mother, grandfather and brother of patient 1, while it is not detected in father of patient 2 and mother's DNA wasn't available. PMID:29879922 (2018) reported a South African family of mixed descent in which all affetced first generation (G1) members presented with a predominant distal ‘posterior calf’ myopathy starting in early adulthood. Their offspring (G2) experienced severe unexpected symptoms of myalgia and cramps since adolescence. All affected G1 individuals were homozygous for a novel truncating p.Tyr1433Ter DYSF variant, with their asymptomatic sibling and pauci-symptomatic G2 offspring carrying only a single variant allele. PMID:35962550 (2022) reported a large family with progressive muscular dystrophy and hyperCKaemia and was identified with a monoallelic novel DYSF variant (p.Tyr2070Metfs*4). Skeletal muscle involvement was milder and later onset than typical dysferlinopathy presentations; these clinical signs manifested in four individuals, all between the fourth and sixth decades of life. The study showed a consistent dysferlinopathy phenotype across three generations, with dystrophic muscle changes and fatty replacement, reduced dysferlin protein expression, but no evidence that the C‑terminal DYSF variant triggers mRNA decay. Monoallelic DYSF variants are not yet associated with any phenotypes in OMIM.; Changed rating: GREEN; Changed publications to: 17287450, 21658164, 29879922, 35962550; Changed phenotypes to: Muscular dystrophy, limb-girdle, autosomal recessive 2, OMIM:253601, Miyoshi muscular dystrophy 1, OMIM:254130, Myopathy, distal, with anterior tibial onset, OMIM:606768; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal |
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| Distal myopathies v1.20 | GIPC1 |
Zornitza Stark gene: GIPC1 was added gene: GIPC1 was added to Distal myopathies. Sources: Literature Mode of inheritance for gene: GIPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GIPC1 were set to 32413282 Phenotypes for gene: GIPC1 were set to Oculopharyngodistal myopathy-2 (OPDM2), MIM#618940 Mode of pathogenicity for gene: GIPC1 was set to Other Review for gene: GIPC1 was set to GREEN Added comment: 19 families reported with heterozygous trinucleotide repeat expansion in the 5-prime untranslated region and onset of distal muscle weakness, mainly of the lower limbs, and/or ophthalmoplegia in the second or third decades of life. Note this is unlikely to be tractable currently by most NGS assays, and may be best dealt with as an STR disorder here. Sources: Literature |
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| Distal myopathies | DES | Arianna Tucci marked DES as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Distal myopathies | DES | Arianna Tucci classified DES as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Distal myopathies | DES | Arianna Tucci reviewed DES | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||