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ã 2002 Nature Publishing Group

European Journal of Human Genetics (2002) 10, 162 ± 166
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ARTICLE

Postaxial polydactyly type A/B (PAP-A/B) is linked to chromosome 19p13.1-13.2 in a chinese kindred
Hongshan Zhao1,3, Yong Tian1,3, Guido Breedveld2, Shangzhi Huang1, Ying Zou1, Jue Y1, Jinghua Chai1, Hui Li1, Mingyue Li1, Ben AOostra2, Wilson HY Lo1 and Peter Heutink*,2
Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, WHO Collaboration Center of Community Control for Inherited Diseases, Beijing, People's Republic of China; 2Department of Clinical Genetics, Erasmus University Rotterdam, Rotterdam, The Netherlands Postaxial polydactylyis characterised by fifth digit duplications in hands and/or feet. Two phenotypic varieties have been described. In type A, the extra digit is well formed and articulates with the fifth or an extra metacarpal. A rudimentary extra fifth digit characterises type B. Mutations in the GLI3 gene are associated with postaxial polydactyly in some families and a second locus has been identified onchromosome 13 but the majority of cases remain unexplained. We report here a third locus for postaxial polydactyly on chromosome 19p13.1-13.2 in a large Chinese kindred with a combination of type A and B. Two-point linkage analysis showed the highest LOD score (Zmax = 5.85 at y = 0 cM) at marker D19S221. Recombination events with markers D19S1165 and D19S929 define the critical region for this postaxialpolydactyly locus to a region of 4.3 cM on the genetic map. European Journal of Human Genetics (2002) 10, 162 ± 166. DOI: 10.1038/sj/ejhg/5200790 Keywords: postaxial polydactyly; linkage; chromosome 19p13.1-13.2 Introduction
Postaxial polydactyly (PAP) is a frequent congenital hand malformation characterized by fifth digit duplications in hands and/or feet. The prevalence estimates range from1/630 to 1/3300 in Caucasians and from 1/100 to 1/300 in Blacks.1 Two phenotypic varieties have been described, in type A (PAP-A); the extra digit is well formed and articulates with the fifth or an extra metacarpal. Type B (PAP-B) is characterised by a rudimentary extra fifth digit (pedunculated postminimus) and is usually represented by an extra skin tag. Estimates for the penetrance values forPAP-A vary between 63 and 100% and for PAP-B around 48%.2,3,4 PAP can segregate as an autosomal dominant or recessive trait, and is often observed in association with other syndromes.5 ± 10 Partial cutaneous syndactyly of the 4th and 5th digit is often seen in combination with PAP. Genetic studies on families with isolated PAP have revealed at least two autosomal dominant loci responsible for thephenotype. In a large Indian kindred with PAP-A with complete penetrance, Radhakrishna et al.11 found a frameshift mutation in the Gli3 gene on chromosome 7 (PAPA1) [MIM 174200]. A second candidate region for PAP was indicated by the observation that PAP occurs in approximately 75% of trisomy 13 cases.12 Subsequently, a locus for an autosomal dominant PAP-A with reduced penetrance was mapped tochromosome 13q in a large Turkish kindred (PAPA2) [MIM 602085].10 PAP-A and B sometimes occur in the same family and it has been suggested that a single gene might be responsible for both types of polydactyly.13 ± 16 Recently this suggestion was confirmed by the finding that mutations in GLI3 are associated with PAP-A and B within a single family.17 In this study we describe a large kindred from thenorthern part of China, with a combination of autosomal dominant PAP-A and B with incomplete penetrance. Linkage of the phenotype to chromosomes 7 and 13q could be excluded. Subsequently a genome wide search with highly informative
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*Correspondence: P Heutink, Department of Clinical Genetics, Erasmus Medical Center Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. Tel: +31-104088136;...