An incompletely penetrant novel MAFB (p.Ser56Phe) variant in autosomal dominant multicentric carpotarsal osteolysis syndrome

被引:21
作者
Dworschak, Gabriel C. [1 ]
Draaken, Markus [1 ,2 ]
Hilger, Alina [1 ]
Born, Mark [3 ]
Reutter, Heiko [1 ,4 ]
Ludwig, Michael [5 ]
机构
[1] Univ Hosp Bonn, Inst Human Genet, D-53127 Bonn, Germany
[2] Univ Hosp Bonn, Dept Genom, Life & Brain Ctr, D-53127 Bonn, Germany
[3] Univ Hosp Bonn, Dept Pediat Radiol, Childrens Hosp, D-53127 Bonn, Germany
[4] Univ Hosp Bonn, Dept Neonatol, D-53127 Bonn, Germany
[5] Univ Hosp Bonn, Dept Clin Chem & Clin Pharmacol, D-53127 Bonn, Germany
关键词
carpal bones; osteolysis; skeletal dysplasia; tarsal bones; V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) gene; incomplete penetrance; modifier gene; SEGMENTATION GENE; EXPRESSION; KREISLER; DIFFERENTIATION; REVEALS; DOMAIN;
D O I
10.3892/ijmm.2013.1373
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare autosomal dominant skeletal dysplasia usually presenting in early childhood with variable phenotypic features and course. Clinical manifestations comprise aggressive osteolysis of the carpal and tarsal bones in particular, an often progressive nephropathy leading to end-stage renal disease, craniofacial anomalies and mental impairment. Recently, heterozygous missense mutations in the V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) (MAFB) gene have been causally related to MCTO patients in 13 unrelated families investigated. Contrary to these findings suggesting complete penetrance, in the present study, we identified a novel missense MAFB variant present not only in the patient, but also in his unaffected mother, sister and maternal grandmother. This observation demonstrates an incomplete penetrance for some MAFB mutations, thereby suggesting that modifier genes, epigenetic mechanisms or environmental factors may modulate the MCTO phenotype. This should be considered in diagnosis and genetic counseling.
引用
收藏
页码:174 / 178
页数:5
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