Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the Study of Canadian Genetic Isolates.

Hereditary sensory and autonomic neuropathy (HSAN) type II is an autosomal recessive disorder characterized by impairment of pain, temperature, and touch sensation owing to reduction or absence of peripheral sensory neurons. We identified two large pedigrees segregating the disorder in an isolated population living in Newfoundland and performed a 5-cM genome scan. Linkage analysis identified a locus mapping to 12p13.33 with a maximum LOD score of 8.4. Haplotype sharing defined a candidate interval of 1.06 Mb containing all or part of seven annotated genes, sequencing of which failed to detect causative mutations. Comparative genomics revealed a conserved ORF corresponding to a novel gene in which we found three different truncating mutations among five families including patients from rural Quebec and Nova Scotia. This gene, termed "HSN2," consists of a single exon located within intron 8 of the PRKWNK1 gene and is transcribed from the same strand. The HSN2 protein may play a role in the development and/or maintenance of peripheral sensory neurons or their supporting Schwann cells.

Development of a nonsurgical diagnostic tool for endometriosis based on the detection of endometrial leukocyte subsets and serum CA-125 levels.

OBJECTIVE: To determine whether the proportion of several leukocyte subsets is modulated in the endometrium of patients with endometriosis and, if yes, whether it can be used for diagnostic purposes. DESIGN: Case-control study. SETTING: Eight clinical institutions of the Montreal area. PATIENT(S): Women who underwent laparoscopy or laparotomy between 1997 and 2001, who had regular menstrual cycles and were not under hormone treatment for the previous 3 months were selected. This study included 368 women, 173 with surgically confirmed endometriosis and 195 controls with no surgical evidence of endometriosis. MAIN OUTCOME MEASURE(S): Cytometry analysis was used to measure the proportion of several leukocyte subsets among CD45(+) endometrial cells. RESULT(S): The proportion of CD3(+), CD16(+), CD3(-)HLADR(-), CD3(-)CD45RA(-), CD3(+)CD16(-), CD3(+)CD56(-), CD56(-)CD16(+), and CD16b(+) leukocytes was significantly altered in the endometrium of cases compared with controls. A multiple logistic regression model was adjusted with these endometrial leukocytes, serum CA-125 levels, risk factors, and confounders. The diagnostic performance of this predictive model was defined by a specificity of 95% and a sensitivity of 61%. Furthermore, the positive and negative predictive values were 91% and 75%, respectively. CONCLUSION(S): This predictive model represents a novel diagnostic tool to identify women with a high likelihood of suffering from endometriosis.