PDF(Pubmed)
Abstract：
Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare, frequently misdiagnosed, autosomal dominant disease caused by mutations in the FTL gene. It causes bilateral pediatric cataract and hyperferritinemia without iron overload. The objective of this case series, describing three Brazilian families, is to increase awareness of HHCS, as well as to discuss possible phenotypic interactions with concurrent mutations in HFE, the gene associated with autosomal recessive inheritance hereditary hemochromatosis. Whole-exome sequencing was performed in eight individuals with HHCS from three different families, as well as one unaffected member from each family for trio analysis-a total of eleven individuals. Ophthalmological and clinical genetic evaluations were conducted. The likely pathogenic variant c.-157G>A in FTL was found in all affected individuals. They presented slowly progressing bilateral cataract symptoms before the age of 14, with a phenotype of varied bilateral diffuse opacities. Hyperferritinemia was present in all affected members, varying from 971 ng/mL to 4899 ng/mL. There were two affected individuals with one concurrent pathogenic variant in HFE (c.187C>G, p.H63D), who were also the ones with the highest values of serum ferritin in our cohort. Few publications describe individuals with pathogenic mutations in both FTL and HFE genes, and further studies are needed to assess possible phenotypic interactions causing higher values of hyperferritinemia.
摘要：
遗传性高铁蛋白血症-白内障综合征（HHCS）是一种罕见的，经常误诊,由FTL基因突变引起的常染色体显性疾病。它会导致双侧小儿白内障和高铁蛋白血症，而没有铁超负荷。这个案例系列的目的，描述了三个巴西家庭，是提高对HHCS的认识，以及讨论与HFE中并发突变的可能表型相互作用，与常染色体隐性遗传遗传性血色素沉着病相关的基因。在来自三个不同家庭的八个患有HHCS的个体中进行了全外显子组测序，以及每个家庭的一名未受影响的成员进行三人分析-总共11个人。进行了眼科和临床遗传评估。在所有受影响的个体中都发现了FTL中可能的致病性变异c.-157G>A。他们在14岁之前表现出缓慢进展的双侧白内障症状，表现为双侧弥漫性混浊。所有受影响的成员都存在高铁蛋白血症，从971ng/mL到4899ng/mL不等。有两个受影响的个体在HFE中具有一个并发致病变异(c.187C>G，p.H63D),他们也是我们队列中血清铁蛋白最高的人。很少有出版物描述在FTL和HFE基因中具有致病性突变的个体。需要进一步的研究来评估可能导致高铁蛋白血症的表型相互作用。
