OBJECTIVES: To determine linkage in a pedigree with palmoplantar keratoderma (PPK) associated with squamous cell carcinoma of the esophagus. DESIGN: A large American pedigree was studied and the clinical phenotype was described. Linkage analysis was performed using genomic DNA from key individuals. SETTING: A community-based family study. PATIENTS: The family pedigree was expanded from a single index case. MAIN OUTCOME MEASURES: To demonstrate linkage and the relative risk of squamous cell carcinoma of the esophagus in this pedigree. RESULTS: Focal PPK was inherited as an autosomal dominant with variable expression, but signs were not limited to the palmoplantar epidermis. The generalized nature of this pattern of PPK was highlighted by the perifollicular papules and oral hyperkeratosis. Affected individuals (125 individuals) in 7 generations were identified, with 17 affected individuals having associated cancer. Seven of the 8 squamous cell carcinomas of the esophagus occurred in smokers. Other tumors were seen in nonsmokers, but these were not significantly increased. The combined male-female expected incidence of squamous cell carcinoma of the mouth and esophagus was 0.21; observed, 8 (relative risk of 38; P < .001). Linkage to the tylosis and esophageal cancer gene locus on 17q24 was demonstrated with a maximum 2-point lod score of 8.20 at zero recombination fraction for the DNA marker D17S1603. CONCLUSION: The distinctive clinical phenotype in this family suggests a new classification for PPKs, in particular a reappraisal of the phenotype as a focal PPK. A very similar phenotype is found in patients with keratin K16 gene mutations.
OBJECTIVES: To determine linkage in a pedigree with palmoplantar keratoderma (PPK) associated with squamous cell carcinoma of the esophagus. DESIGN: A large American pedigree was studied and the clinical phenotype was described. Linkage analysis was performed using genomic DNA from key individuals. SETTING: A community-based family study. PATIENTS: The family pedigree was expanded from a single index case. MAIN OUTCOME MEASURES: To demonstrate linkage and the relative risk of squamous cell carcinoma of the esophagus in this pedigree. RESULTS: Focal PPK was inherited as an autosomal dominant with variable expression, but signs were not limited to the palmoplantar epidermis. The generalized nature of this pattern of PPK was highlighted by the perifollicular papules and oral hyperkeratosis. Affected individuals (125 individuals) in 7 generations were identified, with 17 affected individuals having associated cancer. Seven of the 8 squamous cell carcinomas of the esophagus occurred in smokers. Other tumors were seen in nonsmokers, but these were not significantly increased. The combined male-female expected incidence of squamous cell carcinoma of the mouth and esophagus was 0.21; observed, 8 (relative risk of 38; P < .001). Linkage to the tylosis and esophageal cancer gene locus on 17q24 was demonstrated with a maximum 2-point lod score of 8.20 at zero recombination fraction for the DNA marker D17S1603. CONCLUSION: The distinctive clinical phenotype in this family suggests a new classification for PPKs, in particular a reappraisal of the phenotype as a focal PPK. A very similar phenotype is found in patients with keratin K16 gene mutations.
Authors: Y Zhang; T Lundgren; S Renvert; D N Tatakis; E Firatli; C Uygur; P S Hart; M C Gorry; J J Marks; T C Hart Journal: J Med Genet Date: 2001-02 Impact factor: 6.318
Authors: A Martinez-Mir; A Zlotogorski; D Londono; D Gordon; A Grunn; E Uribe; L Horev; I M Ruiz; N O Davalos; O Alayan; J Liu; T C Gilliam; J C Salas-Alanis; A M Christiano Journal: J Med Genet Date: 2003-12 Impact factor: 6.318
Authors: T C Hart; P S Hart; D W Bowden; M D Michalec; S A Callison; S J Walker; Y Zhang; E Firatli Journal: J Med Genet Date: 1999-12 Impact factor: 6.318
Authors: P S Hart; Y Zhang; E Firatli; C Uygur; M Lotfazar; M D Michalec; J J Marks; X Lu; B J Coates; W K Seow; R Marshall; D Williams; J B Reed; J T Wright; T C Hart Journal: J Med Genet Date: 2000-12 Impact factor: 6.318
Authors: Joanne E Langan; Charlotte G Cole; Elisabeth J Huckle; Shaun Byrne; Fiona E McRonald; Lynn Rowbottom; Anthony Ellis; Joan M Shaw; Irene M Leigh; David P Kelsell; Ian Dunham; John K Field; Janet M Risk Journal: Hum Genet Date: 2004-03-09 Impact factor: 4.132