Forsythe Elizabeth, Kenny Joanna, Bacchelli Chiara, Beales Philip L
Genetics and Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Front Pediatr. 2018 Feb 13;6:23. doi: 10.3389/fped.2018.00023. eCollection 2018.
Bardet-Biedl syndrome is a rare autosomal recessive multisystem disorder caused by defects in genes encoding for proteins that localize to the primary cilium/basal body complex. Twenty-one disease-causing genes have been identified to date. It is one of the most well-studied conditions in the family of diseases caused by defective cilia collectively known as ciliopathies. In this review, we provide an update on diagnostic developments, clinical features, and progress in the management of Bardet-Biedl syndrome. Advances in diagnostic technologies including exome and whole genome sequencing are expanding the spectrum of patients who are diagnosed with Bardet-Biedl syndrome and increasing the number of cases with diagnostic uncertainty. As a result of the diagnostic developments, a small number of patients with only one or two clinical features of Bardet-Biedl syndrome are being diagnosed. Our understanding of the syndrome-associated renal disease has evolved and is reviewed here. Novel interventions are developing at a rapid pace and are explored in this review including genetic therapeutics such as gene therapy, exon skipping therapy, nonsense suppression therapy, and gene editing. Other non-genetic therapies such as gene repurposing, targeted therapies, and non-pharmacological interventions are also discussed.
巴德-比埃尔综合征是一种罕见的常染色体隐性多系统疾病，由编码定位于初级纤毛/基体复合体的蛋白质的基因突变引起。迄今为止，已鉴定出21个致病基因。它是由纤毛缺陷共同导致的疾病家族中研究最为深入的病症之一，这类疾病统称为纤毛病。在本综述中，我们提供了巴德-比埃尔综合征诊断进展、临床特征及治疗进展的最新情况。包括外显子组和全基因组测序在内的诊断技术进步正在扩大被诊断为巴德-比埃尔综合征的患者范围，并增加诊断存在不确定性的病例数量。由于诊断技术的发展，少数仅具有巴德-比埃尔综合征一两种临床特征的患者也被诊断出来。我们对该综合征相关肾脏疾病的认识不断发展，在此进行综述。新型干预措施正在迅速发展，本综述对其进行了探讨，包括基因治疗、外显子跳跃疗法、无义抑制疗法和基因编辑等基因治疗方法。还讨论了其他非基因治疗方法，如药物重新利用、靶向治疗和非药物干预措施。
