A recurrent de novo DYNC1H1 tail domain mutation causes spinal muscular atrophy with lower extremity predominance, learning difficulties and mild brain abnormality
| Autor: | Sophelia H. S. Chan, Inger Johanne Thuestad, Aad Verrips, Brian H.Y. Chung, Janice Ip, Erik-Jan Kamsteeg, Christopher C.Y. Mak, Nens van Alfen, Angel On-Kei Chan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cytoplasmic Dyneins Male Pathology medicine.medical_specialty Adolescent Biceps Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Muscle hypertrophy Muscular Atrophy Spinal 03 medical and health sciences 0302 clinical medicine medicine Missense mutation Spinal muscular atrophy with lower extremity predominance Humans Child Muscle Skeletal Genetics (clinical) Muscle biopsy medicine.diagnostic_test business.industry Learning Disabilities Lower limb muscle weakness Brain Spinal muscular atrophy medicine.disease Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] Magnetic Resonance Imaging 030104 developmental biology Neurology Pediatrics Perinatology and Child Health Mutation Female Neurology (clinical) Abnormality business 030217 neurology & neurosurgery |
| Zdroj: | Neuromuscular Disorders, 28, 750-756 Neuromuscular Disorders, 28, 9, pp. 750-756 |
| ISSN: | 0960-8966 |
| Popis: | Item does not contain fulltext We describe four unrelated patients with the same de novo heterozygous missense mutation c.751C>T in the DYNC1H1 gene. We found a high phenotype-genotype correlation with all four patients having early childhood-onset predominant lower limb muscle weakness and wasting which was slowly progressing and later-onset mild upper extremities proximal weakness. All four patients presented minor cognitive dysfunction with learning difficulty and developmental behavioural comorbidities with mild abnormalities in the brain MRI. The leg muscle MRI findings are highly consistent in DYN1CH1-related spinal muscular atrophy with lower limb predominance (SMALED) with relative sparing of biceps femoris and semitendinosus, and hypertrophy of adductor longus in the thighs; and sparing the anterior and medial muscles in the calves. This report provides important clinical evidence indicating the de novo heterozygous missense mutation c.751C>T in the DYNC1H1 gene is pathogenic causing SMALED. Muscle MRI is more specific than muscle biopsy in the diagnosis of SMALED. |
| Databáze: | OpenAIRE |
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