Homozygous intronic variants in TPM2 cause recessively inherited Escobar variant of multiple pterygium syndrome and congenital myopathy
| Autor: | Anna Sarkozy, Azzam Ismail, Rahul Phadke, R. Mein, Anne-Marie Childs, Emma Hobson, Karen Pysden, Schaida Schirwani, Francesco Muntoni, Audrey Smith |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Proband Heterozygote Myotonia Congenita Tropomyosin TPM2 Consanguinity 03 medical and health sciences Exon 0302 clinical medicine medicine Humans Abnormalities Multiple Genetics (clinical) Exome sequencing Sequence (medicine) Arthrogryposis Genetics business.industry Homozygote Infant Newborn Infant medicine.disease Congenital myopathy Phenotype 030104 developmental biology Neurology Child Preschool Mutation Pediatrics Perinatology and Child Health Skin Abnormalities RNA Splice Sites Neurology (clinical) Multiple pterygium syndrome medicine.symptom Malignant Hyperthermia business 030217 neurology & neurosurgery |
| Zdroj: | Neuromuscular Disorders. 31:359-366 |
| ISSN: | 0960-8966 |
| DOI: | 10.1016/j.nmd.2020.09.033 |
| Popis: | Pathogenic variants in TPM2 have been associated with a variable clinical spectrum, including congenital myopathies and distal arthrogryposis, all but one with dominant inheritance. We report the second case of recessively inherited TPM2-related Escobar variant of multiple pterygium syndrome and congenital myopathy in a patient from a consanguineous family. Ultra-structural examination of the biopsy revealed few cores/mini-cores and sparse nemaline rods. We found a novel homozygous intronic sequence variant, c.564–2A>C in TPM2. This variant is predicted to abolish the consensus acceptor splice site for exon 6b of TPM2 gene. Parents of the proband, both healthy adults with no clinical features, were heterozygous for the variant. Here we establish a homozygous intronic variant in TPM2 as the likely cause of Escobar variant of multiple pterygium syndrome and congenital myopathy, with sparse nemaline rods. |
| Databáze: | OpenAIRE |
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