Genetic and linkage analysis of familial congenital hypothyroidism: exclusion of linkage to the TSH receptor gene |
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Authors: | B Edman Ahlbom Muhammad Yaqoob Agne Larsson Adam Ilicki Göran Annerén C Wadelius |
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Institution: | Department of Clinical Genetics, Uppsala University Hospital, S-751 85 Uppsala, Sweden Fax: +46-18-554?025; e-mail: bodil.edman@klingen.uu.se, SE Department of Pediatrics, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden, SE Department of Pediatrics, St G?ran’s Children’s Hospital, Karolinska Institute, S-171 77 Stockholm, Sweden, SE
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Abstract: | Congenital hypothyroidism affects 1/3000– 4000 newborns. The causes of this group of disorders are still largely unknown.
Although most cases are sporadic, some families have several affected children and/or consanguineous parents, suggesting autosomal
recessive inheritance. Furthermore, there is a murine strain (hyt) with congenital hypothyroidism and autosomal recessive
inheritance, whose phenotype appears to be identical with the corresponding human disease. In the hyt mouse, the disease is
caused by a mutation in the thyroid-stimulating hormone receptor (TSHR) gene, making this gene a likely candidate also for
the human disease. The human TSHR gene was mapped on radiation hybrid panels and closely linked flanking markers D14S287 and
D14S616 were identified. On the Genebridge 4 panel, D14S287 was found to be located 8.5 cR (corresponding to 2.3 cM) proximal
to the TSHR gene, and D14S616 was found to be located 4.4 cR (1.2 cM) distal to the TSHR gene. These markers were analyzed
in 23 families, most of them with two or more children affected by congenital hypothyroidism and some with appreciable consanguinity
of the parents. Assuming homogeneity, the two-point lod score at θ = 0.1 was –4.8 for D14S287 and –5.8 for D14S616, and thus
linkage to the TSHR gene was excluded. Even when the data were analyzed with allowance for heterogeneity, there was no evidence
of linkage. Our conclusion is that if mutation of the TSHR gene causes familial congenital hypothyroidism in humans, it affects
only a small proportion of the cases.
Received: 8 July 1996 |
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