¹Department of Medical Genetics, Institute of Medical Biochemistry and Genetics, Panum Institute, University of Copenhagen, Denmark

²Biomedical Sciences Division, Department of Genetics, Cerrahpasa Medical Faculty, Istanbul University, Turkey

³Department of Human Genetics, University Hospital Nijmegen, The Netherlands

⁴Department of Clinical Genetics, Aarhus University Hospital, University of Aarhus, Denmark

⁵Institute of Medical Biology and Human Genetics, University of Innsbruck, Austria

⁶Max-Planck Institute of Molecular Genetics, Berlin, Germany

^aCorrespondence: Niels Tommerup, Dept of Medical Genetics, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. Tel: +45 35327826; Fax: +45 35327845; Email: tommerup@imbg.ku.dk

The nail patella syndrome (NPS1) is an autosomal dominant disorder characterised by dysplasia of the finger nails and skeletal abnormalities. NPS1 has been mapped to 9q34, to a 1 cM interval between D9S315 and the adenylate kinase gene (AK1). We have mapped the breakpoints within the candidate NPS1 region in two unrelated patients with balanced translocations. One patient [46,XY,t(1;9)(q32.1;q34)] was detected during a systematic survey of old cytogenetic files in Denmark and southern Sweden. The other patient [46,XY,t(9;17)(q34.1;q25)] was reported previously. D9S315 and AK1 were used to isolate YACs, from which endclones were used to isolate PACs. Two overlapping PAC clones span the 9q34 breakpoints in both patients, suggesting that NPS1 is caused by haploinsufficiency due to truncation or otherwise inactivation of a gene at or in the vicinity of the breakpoints.

nail patella syndrome; NPS1; PAC; YAC; extended DNA; FISH; fine mapping