A short in-frame deletion in NTRK1 tyrosine kinase domain caused by a novel splice site mutation in a patient with congenital insensitivity to pain with anhidrosis

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease characterized by the lack of reaction to noxious stimuli and anhidrosis. It is caused by mutations in the NTRK1 gene, which encodes the high affinity tyrosine kinase receptor I for Neurotrophic Growth Factor (NGF). -- Case Presentation: We present the case of a female patient diagnosed with CIPA at the age of 8 months. The patient is currently 6 years old and her psychomotor development conforms to her age (RMN, SPECT and psychological study are in the range of normality). PCR amplification of DNA, followed by direct sequencing, was used to investigate the presence of NTRK1 gene mutations. Reverse transcriptase (RT)-PCR amplification of RNA, followed by cloning and sequencing of isolated RT-PCR products was used to characterize the effect of the mutations on NTRK1 mRNA splicing. The clinical diagnosis of CIPA was confirmed by the detection of two splice-site mutations in NTRK1, revealing that the patient was a compound heterozygote at this gene. One of these alterations, c.574+1G > A, is located at the splice donor site of intron 5. We also found a second mutation, c.2206-2 A > G, not previously reported in the literature, which is located at the splice acceptor site of intron 16. Each parent was confirmed to be a carrier for one of the mutations by DNA sequencing analysis. It has been proposed that the c.574+1G > A mutation would cause exon 5 skipping during NTRK1 mRNA splicing. We could confirm this prediction and, more importantly, we provide evidence that the novel c.2206-2A > G mutation also disrupts normal NTRK1 splicing, leading to the use of an alternative splice acceptor site within exon 17. As a consequence, this mutation would result in the production of a mutant NTRK1 protein with a seven aminoacid in-frame deletion in its tyrosine kinase domain. --Conclusions: We present the first description of a CIPA-associated NTRK1 mutation causing a short interstitial deletion in the tyrosine kinase domain of the receptor. The possible phenotypical implications of this mutation are discussed.

Facilitated advocacy: supporting farmers to have a voice in policy making and the development of service provision

Listening to people, especially those who are poor, and involving them in policy making and decisions about service delivery processes are logical steps in building better services and improving policies aimed at poverty alleviation. This case describes a facilitated advocacy that helped to negotiate and support a role for poor people who farm and fish, to contribute recommendations for changes in services and policies that impact on their lives. The national Government of India’s Department of Animal Husbandry and Dairying and the Indian Council for Agricultural Research, both in the capital Delhi, have been linking with farmers and fishers and state government officials in the eastern states of Jharkhand, Orissa and West Bengal, in partnership with the STREAM Initiative of the intergovernmental Network of Aquaculture Centers in Asia Pacific and with the support of the UK Government Department for International Development, Natural resources Systems Program supporting farmers to have a voice(13 p.)

Impact of depressive symptoms on subjective well-being: the importance of patient-reported outcomes in schizophrenia

Objective: The subjective experience of psychotic patients toward treatment is a key factor in medication adherence, quality of life, and clinical outcome. The aim of this study was to assess the subjective well-being in patients with schizophrenia and to examine its relationship with the presence and severity of depressive symptoms. Methods: A multicenter, cross-sectional study was conducted with clinically stable outpatients diagnosed with schizophrenia. The Subjective Well-Being under Neuroleptic Scale - short version (SWN-K) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to gather information on well-being and the presence and severity of depressive symptoms, respectively. Spearman's rank correlation was used to assess the associations between the SWN-K total score, its five subscales, and the CDSS total score. Discriminative validity was evaluated against that criterion by analysing the area under the curve (AUC). Results: Ninety-seven patients were included in the study. Mean age was 35 years (standard deviation = 10) and 72% were male. Both the total SWN-K scale and its five subscales correlated inversely and significantly with the CDSS total score (P < 0.0001). The highest correlation was observed for the total SWN-K (Spearman's rank order correlation [ rho] = -0.59), being the other correlations: mental functioning (-0.47), social integration (-0.46), emotional regulation (-0.51), physical functioning (-0.48), and self-control (-0.41). A total of 33 patients (34%) were classified as depressed. Total SWN-K showed the highest AUC when discriminating between depressive severity levels (0.84), followed by emotional regulation (0.80), social integration (0.78), physical functioning and self-control (0.77), and mental functioning (0.73). Total SWN-K and its five subscales showed a significant linear trend against CDSS severity levels (P < 0.001). Conclusion: The presence of moderate to severe depressive symptoms was relatively high, and correlated inversely with patients' subjective well-being. Routine assessment of patient-reported measures in patients with schizophrenia might reduce potential discrepancy between patient and physician assessment, increase therapeutic alliance, and improve outcome.

Um estudo sobre a construção do diagnóstico de autismo nas comunidades da rede de relacionamento do Orkut no Brasil

O processo de construção de diagnósticos na contemporaneidade vem sofrendo modificações, constituindo novo foco de trabalho no campo da sociologia médica. O surgimento de grupos de reivindicação de direitos de pacientes e familiares, no final do século XX, determina um novo elemento na criação de categorias diagnósticas. Ao divulgar conhecimento sobre a experiência do doente, e reivindicar tratamentos, esses grupos desafiam a noção de exclusividade do conhecimento médico sobre os diagnósticos. Nesse sentido, a Internet se mostra um terreno fértil de propagação de conhecimento e de mobilização social, tanto de contestação quanto de afirmação do saber médico. Este trabalho faz uma análise do conteúdo de seis comunidades brasileiras de autismo da rede de relacionamentos do Orkut. Alguns resultados são apresentados em relação à divulgação de modelos teóricos, conhecimento baseado no cotidiano de pacientes e formas de ativismo em saúde nessas comunidades virtuais.