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A new susceptibility locus for hypospadias on chromosome 7q32.2-q36.1

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Abstract

Hypospadias is a common malformation (1/300 boys) where the urethra opens on the ventral side of the penis. It is considered a complex disorder with both genetic and environmental factors involved in the pathogenesis. To identify the chromosomal loci involved in the pathogenesis of hypospadias, we performed a genome-wide linkage analysis in a three-generational family showing autosomal dominant inheritance of hypospadias. Fifteen individuals, whereof seven affected, were genotyped within a total of 426 microsatellite markers and the genotyping results were analyzed using parametric and non-parametric linkage analyses. The genome-wide linkage analysis and subsequent fine mapping gave a maximum linkage in both parametric (LOD score 2.71) and non-parametric (NPL score 5.01) single-point analyses for marker D7S640. A susceptibility haplotype shared by all affected boys was identified with the centromeric and telomeric boundaries defined by markers D7S2519 and D7S2442, respectively. This suggests a novel hypospadias locus at chromosome 7q32.2-q36.1 that encompasses 18.2 Mb (25 cM) and harbors hundreds of genes. Mutation analysis of two genes within the region, the AKR1D1 (aldo-keto reductase family 1, member D1) gene involved in the androgen pathway and the PTN gene coding for pleiotrophin, an embryonic differentiation and growth factor, was performed but without putative findings.

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Authors and Affiliations

  1. Department of Molecular Medicine and Surgery, CMM 02, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden

    Hanh T. T. Thai, Cilla Söderhäll, Kristina Lagerstedt, Mir Davood Omrani, Louise Frisén, Johanna Lundin, Ingrid Kockum & Agneta Nordenskjöld

  2. Department of Medical Genetics, Mottahary Hospital, Kashani Ave, Uromia, Iran

    Mir Davood Omrani

  3. Department of Clinical Neurosciences, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    Ingrid Kockum

  4. Pediatric Surgery, Astrid Lindgren Children Hospital, Karolinska University Hospital, Stockholm, Sweden

    Agneta Nordenskjöld

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  1. Hanh T. T. Thai
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  2. Cilla Söderhäll
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  3. Kristina Lagerstedt
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  4. Mir Davood Omrani
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  7. Ingrid Kockum
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  8. Agneta Nordenskjöld
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Correspondence to Agneta Nordenskjöld.

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Hanh T. T. Thai and Cilla Söderhäll have contributed equally to this article.

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Thai, H.T.T., Söderhäll, C., Lagerstedt, K. et al. A new susceptibility locus for hypospadias on chromosome 7q32.2-q36.1. Hum Genet 124, 155–160 (2008). https://doi.org/10.1007/s00439-008-0533-5

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  • DOI: https://doi.org/10.1007/s00439-008-0533-5

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