RT Journal Article
SR Electronic
T1 <em>A</em> novel <em>NGFB</em> point mutation: a phenotype study of heterozygous patients
JF Journal of Neurology, Neurosurgery &amp; Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 188
OP 195
DO 10.1136/jnnp.2007.136051
VO 80
IS 2
A1 J Minde
A1 T Andersson
A1 M Fulford
A1 M Aguirre
A1 I Nennesmo
A1 I Nilsson Remahl
A1 O Svensson
A1 M Holmberg
A1 G Toolanen
A1 G Solders
YR 2009
UL http://jnnp.bmj.com/content/80/2/188.abstract
AB Objective: A family with neurological findings similar to hereditary sensory and autonomic neuropathy type V having a point mutation in the nerve growth factor beta (NGFB) gene was recently described. The homozygous genotype gives disabling symptoms. The purpose of the present study was to evaluate the symptoms in heterozygous patients.Methods: 26 patients heterozygous for the NGFB mutation (12 men, mean age 50 (13–90) years) were examined clinically and answered a health status questionnaire, including the Michigan Neuropathy Screening Instrument (MNSI). 28 relatives (15 men, mean age 44 (15–86) years) without the mutation served as controls in the clinical examination part. 23 of the heterozygotes were examined neurophysiologically and six heterozygous patients underwent a sural nerve biopsy.Results: The heterozygous phenotype ranged from eight patients with Charcot arthropathy starting in adult age and associated with variable symptoms of neuropathy but without complete insensitivity to pain, anhidrosis or mental retardation, to 10 symptom free patients. There was no difference in MNSI between the young heterozygous cases (&lt;55 years old) and the controls. Six of 23 heterozygous patients had impaired cutaneous thermal perception and 11 of 23 had signs of carpal tunnel syndrome. Sural nerve biopsies showed a moderate reduction of both small myelinated (Aδ) and unmyelinated (C) fibres. No apparent correlation of small fibre reduction to symptoms was found.Conclusions: The NGFB mutation in its heterozygous form results in a milder disease than in homozygotes, with a variable clinical picture, ranging from asymptomatic cases to those with Charcot arthropathy appearing in adult age. Particularly age, but perhaps lifestyle factors also, may influence the development of clinical polyneuropathy.