title: Autosomal dominant avascular necrosis of femoral head in two Taiwanese pedigrees and linkage to chromosome 12q13.
abstract: Avascular necrosis of the femoral head (ANFH) is a debilitating disease that commonly leads to destruction of the hip joint in adults. The etiology of ANFH is unknown, but previous studies have indicated that heritable thrombophilia (increased tendency to form thrombi) and hypofibrinolysis (reduced ability to lyse thrombi), alcohol intake, and steroid use are risk factors for ANFH. We recently identified two families with ANFH showing autosomal dominant inheritance. By applying linkage analysis to a four-generation pedigree, we excluded linkage between the family and three genes related to thrombophilia and hypofibrinolysis: protein C, protein S, and plasminogen activator inhibitor. Furthermore, by a genomewide scan, a significant two-point LOD score of 3.45 (recombination fraction [theta] = 0) was obtained between the family with ANFH and marker D12S85 on chromosome 12. High-resolution mapping was conducted in a second family with ANFH and replicated the linkage to D12S368 (pedigree I: LOD score 2.47, theta = 0.05; pedigree II: LOD score 2.81, theta = 0.10). When an age-dependent-penetrance model was applied, the combined multipoint LOD score was 6.43 between D12S1663 and D12S85. Thus, we mapped the candidate gene for autosomal dominant ANFH to a 15-cM region between D12S1663 and D12S1632 on chromosome 12q13.
authors.affiliation: Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chen
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Liu
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Chen
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Lin
authors.forename: Guan-Lu
authors.initials: GL
authors.lastname: Lin
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.forename: Yang-Te
authors.initials: YT
authors.lastname: Lin
authors.forename: Cathy S J
authors.initials: CS
authors.lastname: Fann
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.forename: Kwang-Jen
authors.initials: KJ
authors.lastname: Hsiao
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Tsai
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D005260:Female; D005271:Femur Head Necrosis / Q000235:genetics*; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D013624:Taiwan