Human Genetics

, 118:348

Identification of a locus for nongoitrous congenital hypothyroidism on chromosome 15q25.3-26.1


  • Helmut Grasberger
    • Department of MedicineThe University of Chicago
  • Martine Vaxillaire
    • Institute of Biology and Pasteur InstituteCNRS UMR 8090
  • Silvana Pannain
    • Department of MedicineThe University of Chicago
  • John C. Beck
    • Howard Hughes Medical Institute and the Department of PediatricsUniversity of Iowa
  • Aviva Mimouni-Bloch
    • Schneider Children’s Medical CenterSackler School of Medicine
  • Vincent Vatin
    • Institute of Biology and Pasteur InstituteCNRS UMR 8090
  • Gilbert Vassart
    • IRIBHM and Department of GeneticsUniversite Libre de Bruxelles
  • Philippe Froguel
    • Institute of Biology and Pasteur InstituteCNRS UMR 8090
    • Imperial College Genome Centre and Section of Genomic MedicineImperial College London
    • Department of MedicineThe University of Chicago
    • Department of PediatricsThe University of Chicago
    • Department of Committee on GeneticsThe University of Chicago
Original Investigation

DOI: 10.1007/s00439-005-0036-6

Cite this article as:
Grasberger, H., Vaxillaire, M., Pannain, S. et al. Hum Genet (2005) 118: 348. doi:10.1007/s00439-005-0036-6


Permanent congenital hypothyroidism is the most prevalent inborn endocrine disorder, and principally due to developmental defects leading to absent, ectopic or hypoplastic thyroid gland. Although commonly regarded as sporadic disease, nonsyndromic thyroid hypoplasia has, in rare cases, been attributed to inherited defects in PAX8 and the TSHR gene. The shared clinical picture caused by these defects is a variable degree of thyrotropin resistance (RTSH [MIM 275200]), accompanied in its severe form by thyroid gland hypoplasia. We recently identified six extended kindreds with autosomal dominant RTSH, only one of which was linked to a mutation in the PAX8 candidate gene. Genome wide scans conducted in two of the remaining five families revealed independently significant linkage to chromosome 15q25.3–26.1, with maximum multipoint LOD scores of 8.51 and 4.31. Linkage to this novel locus was replicated (P<0.01) in each of the three remaining kindreds. Fine mapping of key recombinants in the largest family localized the causative gene within a 3 cM/2.9 Mb interval. Thus, we report the first locus for congenital nongoitrous hypothyroidism identified by a genome wide screening approach.


Hypothyroidism; thyrotropin; thyroid stimulating hormone; genetic linkage

Supplementary material

439_2005_36_MOESM1_ESM.pdf (129 kb)
Supplementary material

Copyright information

© Springer-Verlag 2005