Abstract Several previous reports have suggested that autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in a single gene (the PKDH1 gene). Linkage analysis showed a positive linkage for polymorphic markers at the short arm of chromosome 6 (6p) in all families. PKHD1 has not been cloned. Recombinants in the critical region would permit the narrowing of the 6p interval containing the PKHD1 gene, thus facilitating the final identification (cloning) of this gene. Our study included 30 Spanish families. Each family consisted of both parents and at least two chil- dren, with at least one diagnosed with ARPKD by clini- cal and pathological parameters. DNA was obtained and 6p microsatellite markers were used to establish haplo- types for each family. A positive linkage to chromosome 6p was found for all families. In 2 cases, recombinants in the region containing the PKHD1 gene were found. These families will help narrow the size of the 6p region, facilitating the efforts to position and clone the PKHD1 gene. In conclusion, our analysis of Spanish ARPKD families confirms the lack of linkage heterogeneity. This suggests that mutations at a single locus on chromosome 6p21.1-p12 are responsible for the broad clinical spec- trum of variable phenotypes. Key words Autosomal recessive polycystic kidney disease · DNA polymorphisms · Linkage analysis Introduction Autosomal recessive polycystic kidney disease (ARPKD) is one of the most-common hereditary nephropathies in childhood, affecting approximately 1 in 20,000 newborns [1]. Clinical manifestations are frequently seen in utero and include enlargement of kidneys and oligohydramnios, bili- ary dysgenesis, and portal fibrosis [2, 3]. As a result of oli- gohydramnios these patients show the Potter phenotype, characterized by deformities of limbs and spine and pul- monary hypoplasia, among other abnormalities [4, 5]. Most ARPKD patients are diagnosed in the perinatal peri- od, suffer from respiratory insufficiency, and die after birth, while rare manifestations can present in adulthood (after 20 years of age), with clinical symptoms that resem- ble the adult dominant form of polycystic kidney disease (ADPKD). Intrafamilial similarity of clinical manifestations among affected siblings is a characteristic of ARPKD. The existence of families in which patients manifest a severe perinatal form of the disease (compared with oth- ers in which the patients survive the perinatal period without renal replacement therapy) suggested the exis- tence of at least two ARPKD genes [6]. An ARPKD gene, designated PKHD1, has been mapped to chromo- some 6p21.1-p12. No evidence for linkage heterogeneity was found among families showing the full spectrum of renal and hepatic manifestations. This suggests that the entire clinical spectrum of ARPKD can be explained by different mutations of a single gene [7, 8]. The PKHD1 gene was initially mapped between mi- crosatellite markers D6S465 and D6S466, a region that spans about 3.8 cM [8, 9]. More recently, analysis of recombination events with microsatellite markers from chromosome 6p placed the gene within an interval of about 1 cM, flanked by markers D6S1024 and D6S1714 [10, 11]. Several of the sequences that map to V. Alvarez · R. Alvarez · E. Coto ( ✉ ) Istituto Reina Sofía de Investigaciones Nefrológicas-Laboratorio de Genética Molecular, Hospital Central de Asturias, E-33006 Oviedo, Spain Fax: +34-985-273657 S. Málaga Servicio de Nefrología Pediátrica, Hospital Central de Asturias, Oviedo, Spain M. Navarro · L. Espinosa Servicio de Nefrología Pediátrica, Hospital Infantil La Paz, Madrid, Spain E. Hidalgo Hospital Infantil de Badajoz, Badajoz, Spain J. Badía Hospital General de Castellón, Castellón, Spain Pediatr Nephrol (2000) 14:205–207 © IPNA 2000 GENETIC RENAL DISEASE / ORIGINAL ARTICLE Victoria Alvarez · Serafín Málaga Mercedes Navarro · Laura Espinosa · Emilia Hidalgo José Badía · Ruth Alvarez · Eliecer Coto Analysis of chromosome 6p in Spanish families with recessive polycystic kidney disease Received: 15 February 1999 / Revised: 24 June 1999 / Accepted: 25 June 1999