Statistics from Altmetric.com
- AD-CMT2, autosomal dominant Charcot-Marie-Tooth disease
- AR-CMT2, autosomal recessive Charcot-Marie-Tooth disease
- AD-EDMD, autosomal dominant Emery-Dreifuss muscular dystrophy
- AR-EDMD, autosomal recessive Emery-Dreifuss muscular dystrophy
- DCM-CD, dilated cardiomyopathy with conduction defects
- LGMD1B, limb girdle muscular dystrophy type 1B
The LMNA gene encodes two nuclear envelope proteins, lamins A and C, derived from alternative splicing. First identified in autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD),1 mutations in this gene are implicated in up to seven diseases including autosomal recessive EDMD (AR-EDMD),2 limb-girdle muscular dystrophy type 1B (LGMD1B),3 dilated cardiomyopathy with conduction defects (DCM-CD),4,5 autosomal dominant partial lipodystrophy of Dunnigan type,6 autosomal recessive axonal Charcot-Marie-Tooth disease (AR-CMT2),7 mandibuloacral dysplasia,8 and Hutchinson-Gilford progeria syndrome.9,10 In addition, some patients appear to have a combination of these different phenotypes11,12 or a clinical variant including skin abnormalities.13 To extend the clinical spectrum of laminopathies, we report a previously undescribed dominant missense mutation, E33D, identified in LMNA and clinically characterised by the combination of axonal neuropathy with myopathic features, cardiac disease including dilated cardiomyopathy, conduction disturbances and arrhythmia, and leuconychia. The LMNA gene is therefore the first gene implicated in both autosomal dominant and recessive forms of CMT2.
The pedigree of a white family originating from the south west of France is shown in fig 1. The index case (II-5) and his affected daughter (III-13) were neurologically and cardiologically assessed by one of our team; only partial information was available for other affected members through questioning of patient III-13. The clinical features of all the affected members are shown in table 1. The results of nerve electrophysiological examination of patients II-5 and III-13 are shown in table 2. A muscle CT scan performed for patient II-5 showed wasting and marked fatty infiltration predominating in paraspinal, vasti, hamstring, and gastrocnemius muscles (fig 2). Fig 3 shows the fingernails of patients II-5 and III-13, exhibiting leuconychia.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.