Phenotypes of the N88S Berardinelli-Seip congenital lipodystrophy 2 mutation.
Recently, two missense mutations (N88S, S90L) in the Berardinelli-Seip congenital lipodystrophy gene have been identified in autosomal dominant distal hereditary motor neuropathy and Silver syndrome. We report the phenotypic consequences of the N88S mutation in 90 patients of 1 large Austrian family and two unrelated German families. Variation in the clinical and electrophysiological phenotype enabled us to distinguish six subtypes. In 4.4%, the disorder was not penetrant. Twenty percent of the patients were subclinically affected; some of these patients could only be detected by pathological nerve conduction studies. A distal hereditary motor neuropathy type V phenotype characterized by predominant hand muscle involvement was found in 31.1%, whereas 14.5% showed typical Silver syndrome with amyotrophy of the small hand muscles and spasticity of the lower extremities. Moreover, the phenotype present in 20% was compatible with Charcot-Marie-Tooth disease. In 10%, the clinical diagnosis of pure or complicated hereditary spastic paraparesis was made. Electrophysiological studies showed an axonal neuropathy but also chronodispersion of compound motor action potentials and conduction blocks. Sensory nerve conduction studies were rarely pathological. Our study indicates that the dominant N88S mutation in the Berardinelli-Seip congenital lipodystrophy gene 2 leads to a broad spectrum of motor neuron disorders.
Auer-Grumbach
Michaela
M
Institute of Medical Biology and Human Genetics, Medical University Graz, Harachgasse 21/8, A-08010 Graz, Austria. michaela.auergrumbach@meduni-grasz.at
Schlotter-Weigel
Beate
B
Lochmüller
Hanns
H
Strobl-Wildemann
Gertrud
G
Auer-Grumbach
Piet
P
Fischer
Renate
R
Offenbacher
Hans
H
Zwick
Ernst Bernhard
EB
Robl
Tanja
T
Hartl
Gerald
G
Hartung
Hans-Peter
HP
Wagner
Klaus
K
Windpassinger
Christian
C
D000200:Action Potentials / Q000502:physiology / Q000528:radiation effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001216:Asparagine / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D003923:Diabetes Mellitus, Lipoatrophic / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D004558:Electric Stimulation / Q000379:methods; D004576:Electromyography / Q000379:methods; D005192:Family Health; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009431:Neural Conduction / Q000502:physiology / Q000528:radiation effects; D010375:Pedigree; D010641:Phenotype; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D012694:Serine / Q000235:genetics; D012737:Sex Factors
C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits; D012694:Serine; D001216:Asparagine