RESUMO
BACKGROUND: Preaxial polydactyly type IV, also referred as polysyndactyly, has been described in a few syndromes. We present three generations of a family with preaxial polydactyly type IV and other clinical features of Greig cephalopolysyndactyly syndrome (GCPS). METHODS AND RESULTS: Sequencing analysis of the GLI3 coding region identified a novel donor splice site variant NC_000007.14(NM_000168.6):c.473+3A>T in the proband and the same pathogenic variant was subsequently identified in other affected family members. Functional analysis based on Sanger sequencing of the proband's complementary DNA (cDNA) sample revealed that the splice site variant c.473+3A>T disrupts the original donor splice site, thus leading to exon 4 skipping. Based on further in silico analysis, this pathogenic splice site variant consequently results in a truncated protein NP_000159.3:p.(His123Argfs*57), which lacks almost all functionally important domains. Therefore, functional cDNA analysis confirmed that the haploinsufficiency of the GLI3 is the cause of GCPS in the affected family members. CONCLUSION: Despite the evidence provided, pathogenic variants in the GLI3 do not always definitely correlate with syndromic or nonsyndromic clinical phenotypes associated with this gene. For this reason, further transcriptomic and proteomic evaluation could be suggested.
Assuntos
Acrocefalossindactilia/genética , Predisposição Genética para Doença/genética , Proteínas do Tecido Nervoso/genética , Proteína Gli3 com Dedos de Zinco/genética , Acrocefalossindactilia/diagnóstico por imagem , Acrocefalossindactilia/fisiopatologia , Criança , DNA Complementar , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Proteínas do Tecido Nervoso/metabolismo , Linhagem , Fenótipo , Proteômica , Análise de Sequência de DNA , Transcriptoma , Proteína Gli3 com Dedos de Zinco/metabolismoRESUMO
Psoriasis vulgaris is not frequently seen in patients with renal replacement therapy, especially in patients on peritoneal dialysis. Dialysis also has been reported to improve psoriatic skin lesions with a much higher response rate for peritoneal dialysis than haemodialysis. Conversely, we present a case of a man who developed psoriasis after 16 months of peritoneal dialysis. Discontinuation of icodextrin as a possible factor provoking systemic inflammation had no impact on the course of the disease. In this report, we review the existing studies and counsel caution against optimistic expectations of benefits from dialysis in patients with psoriasis.
