SMN1 dosage analysis in spinal muscular atrophy from India

BACKGROUND: Spinal muscular atrophy (SMA) represents the second most common fatal autosomal recessive disorder after cystic fibrosis. Due to the high carrier frequency, the burden of this genetic disorder is very heavy in developing countries like India. As there is no cure or effective treatment, genetic counseling becomes very important in disease management. SMN1 dosage analysis results can be utilized for identifying carriers before offering prenatal diagnosis in the context of genetic counseling. METHODS: In the present study we analyzed the carrier status of parents and sibs of proven SMA patients. In addition, SMN1 copy number was determined in suspected SMA patients and parents of children with a clinical diagnosis of SMA. RESULTS: wenty nine DNA samples were analyzed by quantitative PCR to determine the number of SMN1 gene copies present, and 17 of these were found to have one SMN1 gene copy. The parents of confirmed SMA patients were found to be obligate carriers of the disease. Dosage analysis was useful in ruling out clinical suspicion of SMA in four patients. In a family with history of a deceased floppy infant and two abortions, both parents were found to be carriers of SMA and prenatal diagnosis could be offered in future pregnancies. CONCLUSION: SMN1 copy number analysis is an important parameter for identification of couples at risk for having a child affected with SMA and reduces unwarranted prenatal diagnosis for SMA. The dosage analysis is also useful for the counseling of clinically suspected SMA with a negative diagnostic SMA test

Ataxin 1 and Ataxin 3 in Neuronal Intranuclear Inclusion Disease

Neuronal intranuclear inclusion disease (NIID) is a multisystem neurodegenerative disorder characterized by large intranuclear aggregates in neurons of the central and peripheral nervous system. These ubiquitinated intranuclear inclusions are morphologically similar to the intraneuronal aggregates that have been identified in the CAG/polyglutamine expansion diseases. As rare aggregates in NIID contain a polyglutamine epitope, we further investigated the relationship between this disease and the CAG/polyglutamine expansion diseases. Here, we show that ataxin 1 and ataxin 3 proteins are recruited into aggregates in NIID in the absence of a CAG expansion in the SCA1 and SCA3 genes. These data support an association of NIID with the polyglutamine disorders and provide evidence of in vivo recruitment of proteins with polyglutamine tracts into intraneuronal aggregates

Women in Academic Pathology: Pathways to Department Chair

The Association of Pathology Chairs, an organization of American and Canadian academic pathology departments, has a record percent of women department chairs in its ranks (31%), although still not representative of the percent of women pathology faculty (43%). These women chairs were surveyed to determine what had impeded and what had facilitated their academic advancement before becoming chairs. The 2 most frequently identified impediments to their career advancement were heavy clinical loads and the lack of time, training, and/or funding to pursue research. Related to the second impediment, only one respondent became chair of a department which was in a top 25 National Institutes of Health-sponsored research medical school. Eighty-nine percent of respondents said that they had experienced gender bias during their careers in pathology, and 31% identified gender bias as an important impediment to advancement. The top facilitator of career advancement before becoming chairs was a supportive family. Strikingly, 98% of respondents have a spouse or partner, 75% have children, and 38% had children younger than 18 when becoming chairs. Additional top facilitators were opportunities to attend national meetings and opportunities to participate in leadership. Previous leadership experiences included directing a clinical service, a residency training program, and/or a medical student education program. These results suggest important ways to increase the success of women in academic pathology and increasing the percent of women department chairs, including supporting a family life and providing time, encouragement and resources for research, attending national meetings, and taking on departmental leadership positions