Browsing by Author "Coutinho, Francisca"
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- Does the clinical phenotype of mucolipidosis-IIIγ differ from its αβ counterpart?: supporting facts in a Cohort of 18 patientsPublication . Nampoothiri, Sheela; Elcioglu, Nursel H.; Koca, Suleyman S.; Yesodharan, Dhanya; Kk, Chandrababu; Krishnan, Vinod; Bhat, Meenakshi; Nair K, Mohandas; Radhakrishnan, Natasha; Kappanayil, Mahesh; Sheth, Jayesh J.; Alves, Sandra; Coutinho, Francisca; Friez, Michael J.; Pauli, Richard M.; Unger, Sheila; Superti-Furga, Andrea; Leroy, Jules G.; Cathey, Sara S.Mucolipidosis-IIIγ (ML-IIIγ) is a recessively inherited slowly progressive skeletal dysplasia caused by mutations in GNPTG. We report the genetic and clinical findings in the largest cohort with ML-IIIγ so far: 18 affected individuals from 12 families including 12 patients from India, five from Turkey, and one from the USA. With consanguinity confirmed in eight of 12 families, molecular characterization showed that all affected patients had homozygous pathogenic GNPTG genotypes, underscoring the rarity of the disorder. Unlike ML-IIIαβ, which present with a broader spectrum of severity, the ML-III γ phenotype is milder, with onset in early school age, but nonetheless thus far considered phenotypically not differentiable from ML-IIIαβ. Evaluation of this cohort has yielded phenotypic findings including hypertrophy of the forearms and restricted supination as clues for ML-IIIγ, facilitating an earlier correct choice of genotype screening. Early identification of this disorder may help in offering a timely intervention for the relief of carpal tunnel syndrome, monitoring and surgery for cardiac valve involvement, and evaluation of the need for joint replacement. As this condition may be confused with rheumatoid arthritis, confirmation of diagnosis will prevent inappropriate use of immunosuppressants and disease-modifying agents.
- Gene editing in Lysosomal DiseasesPublication . Duarte, Ana Joana; Bragança, José; Coutinho, Francisca; Amaral, OlgaClustered Regularly Interspaced Short Palindromic Repeats (CRISPR) were found as an immune adaptive mechanism in bacteria and quickly applied to various fields as a gene editing tool. Gene editing methods, as a research tool to attempt in vitro correction, have been carried out in several disorders. Induced pluripotent stem cells (iPSCs) from patients with several genetic diseases, including Lysosomal Storage Diseases (LSDs), have been successfully established. Patient-derived iPSCs present the advantage of having the patient’s genetic background with all corresponding influences on the disease’s mechanism. In LSDs, enzyme replacement therapy (ERT, regular supplementation of the defective enzyme), is the most common treatment to clear the accumulated substrates in patient cells but it is hardly effective in non-neurological disease forms. The CRISPR/Cas9 genome-editing system is most promising for the establishment of disease models and for the potential correction of causal. Gene editing technologies and iPSCs provide a unique system for data analysis and research for target therapy.
- Genética e cérebro na "fábrica de perguntas"Publication . Amaral, Olga; Alves, Sandra; Duarte, Ana; Ribeiro, Diogo; Rocha, Hugo; Coutinho, Francisca; Alves, Mariana; Moreira, Luciana; Matos, LilianaCom esta atividade desenvolvida no âmbito da semana aberta do INSA pretendeu-se demonstrar como a Genética e o cérebro são os centros de controlo do quotidiano. Na parte prática desenvolveram-se atividades "mãos na massa" e "minds on" relacionadas com os temas.