Department of Pediatric Dentistry, School of Dentistry, Aarhus University, Denmark.
Int J Paediatr Dent. 2011 Nov;21(6):407-12. doi: 10.1111/j.1365-263X.2011.01142.x. Epub 2011 Jun 27.
BACKGROUND. Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES. The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study the phenotypic variation of the enamel in affected family members. RESULTS. Significant linkage was found to a locus at chromosome 8q24.3 comprising the gene FAM83H identified to be responsible for ADHCAI in other families. Subsequent sequencing of FAM83H in affected family members revealed a novel nonsense mutation, p.Y302X. Limited phenotypic variation was found among affected family members with loss of translucency and discoloration of the enamel. Extensive posteruptive loss of enamel was found in all teeth of affected subjects. The tip of the cusps on the premolars and molars and a zone along the gingival margin seemed resistant to posteruptive loss of enamel. We have screened FAM83H in another five unrelated Danish patients with a phenotype of ADHCAI similar to that in the five-generation family, and identified a de novo FAM83H nonsense mutation, p.Q452X in one of these patients. CONCLUSION. We have identified a FAM83H mutation in two of six unrelated families with ADHCAI and found limited phenotypic variation of the enamel in these patients.
常染色体显性低钙性牙釉质不全（ADHCAI）是一种具有严重牙齿表现的疾病。
通过全基因组连锁扫描，在一个丹麦五代家系中寻找导致 ADHCAI 表型的基因，并研究受累家系成员的牙釉质表型变异。
在包含 FAM83H 基因的 8q24.3 染色体区域发现了显著的连锁，该基因已被确定为其他家系中 ADHCAI 的致病基因。随后对受累家系成员的 FAM83H 进行测序，发现了一个新的无义突变 p.Y302X。受累家系成员的牙釉质表现出有限的表型变异，表现为半透明性丧失和变色。所有受累者的牙齿均发生广泛的萌出后牙釉质丧失。在切牙和磨牙的牙尖以及沿龈缘的一个区域，牙釉质似乎不易受到萌出后丧失的影响。我们已经在另外五个丹麦无关的 ADHCAI 患者中筛查了 FAM83H，发现其中一个患者存在新的 FAM83H 无义突变 p.Q452X。
我们在两个与 ADHCAI 相关的无关联家系中发现了 FAM83H 突变，并发现这些患者的牙釉质表型变异有限。
