A new locus for a dominant form of multinodular goiter on 3q26.1-q26.3

A mass screening program for congenital hypothyroidism has markedly improved prognosis of children with congenital hypothyroidism and also revealed several cases with unknown pathogenesis. We here report two independent Japanese multigeneration families with multinodular goiter (MNG) with euthyroidism and with high TSH. The propositi, 3- and 8-year-old girls in two families, were found during a mass screening. An autosomal dominant pattern of inheritance was suggested in both families. The clinical examinations suggested impaired hormonogenesis but discarded known defects in iodine transport, organification, deficiency of hydrogen peroxide, and thyroid peroxidase. Linkage analysis of the two families including 10 members each using 343 microsatellite markers mapped a single locus independently at D3S1618 (theta = 0) on 3q26.1-q26.3 with a two-point LOD score 3.62 (1.81 for each family) and multipoint LOD score of 3.61 (1.80 for each family). Haplotype inspection delimited an 18-cM interval between D3S1565 and D3S3686.