mutation in nerve growth factor causes loss of pain perception

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Abstract from Hum Mol Genet. 2004 Feb 19

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

pain perception.

Einarsdottir E, Carlsson A, Minde J, Toolanen G, Svensson O, Solders G,

Holmgren G, Holmberg D, Holmberg M.

Department of Medical Biosciences, Unit of Clinical and Medical

Genetics, Umea University, SE-90187 Umea, Sweden.

Identification of genes associated with pain insensitivity syndromes can

increase the understanding of the pathways involved in pain and

contribute to the understanding of how sensory pathways relate to other

neurological functions. In this report we describe the mapping and

identification of the gene responsible for loss of deep pain perception

in a large family from Northern Sweden. The loss of pain perception in

this family is characterized by impairment in the sensing of deep pain

and temperature but with normal mental abilities and with most other

neurological responses intact. A severe reduction of unmyelinated nerve

fibers and a moderate loss of thin myelinated nerve fibers are observed

in the patients. Thus the cases in this study fall into the class of

patients with loss of pain perception with underlying peripheral

neuropathy. Clinically they best fit into HSAN V. Using a model of

recessive inheritance we identified an 8.3 Mb region on chromosome

1p11.2-p13.2 shared by the affected individuals in the family. Analysis

of functional candidate genes in the disease critical region revealed a

mutation in the coding region of the nerve growth-factor beta (NGFB)

gene specific for the disease haplotype. This NGF mutation seems to

separate the effects of NGF involved in development of central nervous

system functions such as mental abilities, from those involved in

peripheral pain pathways. This mutation could therefore potentially

provide an important tool to study different roles of NGF, and of pain

control.