Davar Gudarz, Shalish Christo, Blumenfeld Anat, Breakefield Xandra O
Molecular Genetics Unit, Neurology Service, Massachusetts General Hospital, Charlestown, MA 02129, USA Neuroscience Program, Harvard Medical School, Boston, MA 02115, USA Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Pain. 1996 Sep;67(1):135-139. doi: 10.1016/0304-3959(96)03113-2.
Hereditary sensory neuropathy Type II (HSN II) is an autosomal recessive disorder characterized by the loss of peripheral sensory modalities in individuals with otherwise normal development. Patients with HSN II often have chronic ulceration of the fingers and toes, autoamputation of the distal phalanges, and neuropathic joint degeneration associated with loss of pain sensation. Recent descriptions of a similar phenotype in mice carrying a targeted mutation in the low affinity nerve growth factor receptor, p75NGFR, suggested the possibility that mutations in this gene or other members of the nerve growth factor (NGF) family of genes and their receptors might be responsible for this human disorder. In this study candidate genes were evaluated by their inheritance pattern in two sisters affected with HSN II, their unaffected sister and mother in a consanguineous family. The segregation of polymorphic alleles at and around loci for p75NGFR, TRKA, TRKB, BDNF, and familial dysautonomia (another hereditary sensory neuropathy having features in common with HSN II) virtually excluded these genes as the cause of HSN II in this family. Further evaluation of loci for other neurotrophic factors and their receptors, which will be possible when mapping information on their loci becomes available, may permit the identification of the gene responsible for HSN II.
遗传性感觉神经病II型（HSN II）是一种常染色体隐性疾病，其特征是个体在发育正常的情况下出现外周感觉功能丧失。HSN II患者常出现手指和脚趾的慢性溃疡、远端指骨的自截以及与痛觉丧失相关的神经性关节退变。最近在携带低亲和力神经生长因子受体p75NGFR靶向突变的小鼠中描述了类似的表型，这表明该基因或神经生长因子（NGF）基因家族的其他成员及其受体的突变可能是导致这种人类疾病的原因。在本研究中，通过一个近亲家庭中两名受HSN II影响的姐妹、她们未受影响的姐妹和母亲的遗传模式对候选基因进行了评估。p75NGFR、TRKA、TRKB、BDNF基因座及其周围以及家族性自主神经功能异常（另一种与HSN II有共同特征的遗传性感觉神经病）的多态性等位基因的分离实际上排除了这些基因是该家族HSN II病因的可能性。当其他神经营养因子及其受体基因座的定位信息可用时，对其进行进一步评估，可能会鉴定出导致HSN II的基因。
