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Recessive truncating IGHMBP2 mutations presenting as axonal sensorimotor neuropathy.
Gudrun Schottmann1, Heinz Jungbluth1, Ulrike Schara1
1From the Department of Neuropediatrics and the NeuroCure Clinical Research Center (G.S., E.K., S.M.G., E.G., F.S., M.S.), and Department of Neuropediatrics/SPZ (K.v.A.), Charité-Universitätsmedizin Berlin, Germany; Department of Paediatric Neurology-Neuromuscular Service (H.J.), Evelina Children's Hospital, St Thomas' Hospital, the Randall Division of Cell and Molecular Biophysics, Muscle Signalling Section and the Department of Clinical Neuroscience, IoP, King's College, London, UK; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics (U.S.), University of Essen, Germany; Department of Neurology (F.N.), King's College Hospital, London; Department of Clinical Genetics (C.D.), Guy's Hospital, London, UK; and Friedrich Baur Institute (J.S.), Department of Neurology, Ludwig Maximilians University Munich, Germany.
Mutations in the IGHMBP2 gene cause hereditary sensorimotor neuropathy, even without respiratory symptoms. This finding expands the known spectrum of IGHMBP2-associated disorders.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Hereditary neuropathies often present diagnostic challenges when known genes are excluded.
- Sensorimotor neuropathy is a debilitating condition with diverse genetic etiologies.
Observation:
- Five patients from three families presented with progressive sensorimotor neuropathy.
- These patients carried truncating mutations in the IGHMBP2 gene.
- Unlike classic cases, respiratory distress was absent in most patients.
Findings:
- Identified novel truncating mutations in the IGHMBP2 gene in patients with sensorimotor neuropathy.
- Demonstrated that IGHMBP2 mutations can cause neuropathy without significant respiratory compromise.
- Pathogenicity was confirmed via mRNA and protein level analysis in patient fibroblasts.
Implications:
- IGHMBP2 mutations should be considered in the genetic diagnosis of hereditary sensorimotor neuropathies.
- Broadens the clinical phenotype associated with IGHMBP2 mutations.
- Highlights the importance of molecular genetic testing in unsolved neuropathy cases.
