A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception

Abstract In Sweden, a large family with a point mutation in the nerve growth factor-beta gene has previously been identified. The carriers of this mutation have reduced small-fibre density and selective deficits in deep pain and temperature modalities. The clinical findings in this population are described as hereditary sensory and autonomic neuropathy type V. The purpose of the current study was to investigate the prevalence of carpal tunnel syndrome in hereditary sensory and autonomic neuropathy type V based on clinical examinations and electrophysiological measurements. Furthermore, the cross-sectional area of the median nerve at the carpal tunnel inlet was measured with ultrasonography. Out of 52 known individuals heterozygous for the nerve growth factor-beta mutation in Sweden, 23 participated in the current study (12 males, 11 females; mean age 55 years; range 25–86 years). All participants answered a health questionnaire and underwent clinical examination followed by median nerve conduction study in a case–control design, and measurement of the nerve cross-sectional area with ultrasonography. The diagnosis of carpal tunnel syndrome was made based on consensus criteria using patient history and nerve conduction study. The prevalence of carpal tunnel syndrome in the hereditary sensory and autonomic neuropathy group was 35% or 52% depending on whether those individuals who had classic symptoms of carpal tunnel syndrome but negative nerve conduction studies were included or not. Those who had a high likelihood of carpal tunnel syndrome based on classic/probable patient history with positive nerve conduction study had a significantly larger median nerve cross-sectional area than those who had an unlikely patient history with negative nerve conduction study. The prevalence of carpal tunnel syndrome was 10–25 times higher in individuals heterozygous for the nerve growth factor-beta mutation than the general Swedish population. Further studies are needed to better understand the underlying pathophysiological mechanisms.

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Nerve Growth Factor-Beta, purified from bull seminal plasma, enhances corpus luteum formation and conceptus development in Bos taurus cows

Theriogenology ◽

10.1016/j.theriogenology.2017.10.007 ◽

2018 ◽

Vol 106 ◽

pp. 30-38 ◽

Cited By ~ 11

Author(s):

Jamie L. Stewart ◽

Vitor R.G. Mercadante ◽

Nicholas W. Dias ◽

Igor F. Canisso ◽

Peter Yau ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Corpus Luteum ◽

Seminal Plasma ◽

Bos Taurus ◽

Nerve Growth ◽

Conceptus Development ◽

Growth Factor Beta

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Orthopedic aspects of familial insensitivity to pain due to a novel nerve growth factor beta mutation

Acta Orthopaedica ◽

10.1080/17453670610045911 ◽

2006 ◽

Vol 77 (2) ◽

pp. 198-202 ◽

Cited By ~ 30

Author(s):

Jan Minde ◽

Olle Svensson ◽

Monica Holmberg ◽

Göran Solders ◽

Göran Toolanen

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Nerve Growth ◽

Growth Factor Beta ◽

Insensitivity To Pain

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A Missense Point Mutation in Nerve Growth Factor (NGFR100W) Results in Selective Peripheral Sensory Neuropathy

10.1101/784660 ◽

2019 ◽

Author(s):

Wanlin Yang ◽

Kijung Sung ◽

Wei Xu ◽

Maria J Rodriguez ◽

Andrew C. Wu ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Point Mutation ◽

Pain Perception ◽

Nerve Fibers ◽

Anterior Cingulate ◽

Myelinated Nerve ◽

Nerve Growth ◽

Progressive Loss ◽

Peripheral Sensory

ABSTRACTA missense point mutation in nerve growth factor (NGFR100W) is associated with hereditary sensory autonomic neuropathy V (HSAN V), originally discovered in a Swedish family. These patients develop severe loss of perception to deep pain but with apparently normal cognitive functions. To better understand the disease mechanism, we have generated the first NGFR100Wknockin mouse model of HSAN V. Mice homozygous for the NGFR100Wmutation (NGFfln/fln) showed significant structural deficits in intra-epidermal nerve fibers (IENFs) at birth. These mice had a total loss of pain perception at ∼2 months of age and they often failed to survive to full adulthood. Heterozygous mice (NGF+/fln) developed a progressive degeneration of small sensory fibers both behaviorally and functionally: they showed a progressive loss of IENFs starting at the age of 9 months accompanied with progressive loss of perception to painful stimuli such as noxious temperature. Quantitative analysis of lumbar 4/5 dorsal root ganglia (DRG) revealed a significant reduction in small size neurons positive for calcitonin gene-related peptide, while analysis of sciatic nerve fibers revealed the mutant NGF+/flnmice had no reduction in myelinated nerve fibers. Significantly, the amount of NGF secreted from fibroblasts were reduced in heterozygous and homozygous mice compared to their wild-type littermates. Interestingly, NGF+/flnshowed no apparent structural alteration in the brain: neither the anterior cingulate cortex nor the medial septum including NGF-dependent basal forebrain cholinergic neurons. Accordingly, these animals did not develop appreciable deficits in tests for central nervous system function. Our study provides novel insights into the selective impact of NGFR100Wmutation on the development and function of the peripheral sensory system.

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