RESUMEN
UNLABELLED: We present a case of a fatal Epstein-Barr infection in a 17-year-old male patient suspected to be caused by X-linked lymphoproliferative disease. At the time of hospitalization, DNA diagnostics was not available. The suspected diagnosis was confirmed several years later when a SH2D1A missense mutation was identified in stored patient DNA. Extended pedigree analysis showed that this mutation occurred de novo in his mother. In addition, we provide a summary of the currently listed SH2D1A mutations. CONCLUSION: This case report underlines the importance of DNA storage, pedigree analysis, and multidisciplinary care in patients with rare diseases and their families.
Asunto(s)
ADN/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Trastornos Linfoproliferativos/genética , Mutación , Enfermedades Raras/genética , Adolescente , Adulto , Análisis Mutacional de ADN , Diagnóstico Diferencial , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/metabolismo , Masculino , Linaje , Fenotipo , Proteína Asociada a la Molécula de Señalización de la Activación LinfocitariaRESUMEN
BACKGROUND: Several genetic causes of ectopia lentis (EL), with or without systemic features, are known. The differentiation between syndromic and isolated EL is crucial for further treatment, surveillance and counseling of patients and their relatives. Next generation sequencing (NGS) is a powerful tool enabling the simultaneous, highly-sensitive analysis of multiple target genes. OBJECTIVE: The aim of this study was to evaluate the diagnostic yield of our NGS panel in EL patients. Furthermore, we provide an overview of currently described mutations in ADAMTSL4, the main gene involved in isolated EL. METHODS: A NGS gene panel was analysed in 24 patients with EL. RESULTS: A genetic diagnosis was confirmed in 16 patients (67%). Of these, four (25%) had a heterozygous FBN1 mutation, 12 (75%) were homozygous or compound heterozygous for ADAMTSL4 mutations. The known European ADAMTSL4 founder mutation c.767_786del was most frequently detected. CONCLUSION: The diagnostic yield of our NGS panel was high. Causative mutations were exclusively identified in ADAMTSL4 and FBN1. With this approach the risk of misdiagnosis or delayed diagnosis can be reduced. The value and clinical implications of establishing a genetic diagnosis in patients with EL is corroborated by the description of two patients with an unexpected underlying genetic condition.