RESUMO
BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous group of rare Mendelian skin disorders characterized by cornification and differentiation defects of keratinocytes. Mutations in nine genes including PNPLA1 are known to cause nonsyndromic forms of ARCI. To date, only 10 distinct pathogenic mutations in PNPLA1 have been reported. OBJECTIVES: To identify new causative PNPLA1 mutations. METHODS: We screened genetically unresolved cases, including our ARCI collection, comprising more than 700 families. Screening for mutations was performed either by direct Sanger sequencing or in combination with a multigene panel, followed by sequence and mutation analysis. RESULTS: Here we report on 16 novel mutations present in patients from 17 families. While all previously reported mutations and most of our novel mutations are located within the core patatin domain, we report five novel PNPLA1 mutations that are downstream of this domain. Thus, as recently described for PNPLA2, we hypothesize that a region larger than the core domain is required for full enzymatic activity of PNPLA1 in human skin barrier formation. CONCLUSIONS: We estimate the frequency of PNPLA1 mutations among patients with ARCI to be around 3%. Most of our patients were born as collodion babies and showed a relatively mild ichthyosis phenotype. In four unrelated patients we observed a cyclic scaling course, which seems to be a potential phenotypic variation in a small percentage of patients with PNPLA1 mutations. The variability of the clinical manifestations and the lack of typical clinical features are specific for patients with PNPLA1 mutations, and emphasize the importance of DNA sequencing for differential diagnosis of ARCIs.
Assuntos
Ictiose Lamelar/genética , Lipase/genética , Mutação/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Genes Recessivos/genética , Humanos , Ictiose Lamelar/diagnóstico , Lactente , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Linhagem , Fenômenos Fisiológicos da Pele/genética , Adulto JovemRESUMO
BACKGROUND: As an effective treatment for post-craniotomy epidural haematomas (EDHs), a novel method of urokinase instillation using a closed suction drain is presented and the procedure feasibility and outcomes assessed. METHOD: A closed system, comprising a closed suction drain with a three-spring 200 mL evacuator, fluid bag with urokinase, and syringe, was constructed to instill urokinase and evacuate a postoperative EDH. Nine patients with a symptomatic, localised EDH under a bone flap after a craniotomy underwent successive urokinase instillation following the proposed protocol. Measurement of the EDH volume and clinical evaluation were performed. FINDINGS: An improvement of computerised tomography findings and clinical state after urokinase instillation was observed in all patients. Six urokinase instillations lasting 12 h in 6 patients with an EDH (18.2 +/- 2.4 mL) and 12 urokinase instillations lasting 24 h in the other 3 patients with an EDH (33.0 +/- 7.9 mL) succeeded in achieving a minimal residual EDH (6.1 +/- 2.8 mL). The EDH volume decreased at a rate of 13.0 +/- 2.3 mL/12 h. The GCS scores increased immediately after thrombolytic evacuation of the EDHs in 6 out of the 9 patients. For the other three patients who did not show a change of GCS score, the severe headaches were improved. All the patients were successfully treated using the proposed technique with no procedural complications such as haemorrhage or infection in the operative wound. CONCLUSIONS: This pilot study demonstrated that thrombolytic evacuation of a post-craniotomy EDH using a closed suction drain is feasible without complications and may be associated with better outcomes.
