Ahlbom Bodil Edman, Yaqoob Muhammad, Gustavsson Peter, Abbas Hafez Ghulam, Annerén Göran, Larsson Agne, Wadelius Claes
Department of Genetics and Pathology, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden.
Hum Genet. 2002 Feb;110(2):145-7. doi: 10.1007/s00439-002-0680-z. Epub 2002 Jan 29.
Congenital hypothyroidism affects 1/3000-4000 newborns and it has been estimated that 10-20% are familial cases with an autosomal recessive mode of inheritance. Previous studies of mostly individual cases have led to the identification of mutations in a number of genes, indicating that it is a genetically heterogeneous disease, but no major gene has been identified. In the present investigation, a population-based sample of 23 families with autosomal recessive congenital hypothyroidism, but no signs of goitre, were subject to linkage analysis. When markers located close to the thyroglobulin gene on chromosome 8q24 were used in a two-point analysis allowing for heterogeneity, a Z(max) of 4.10 was obtained with the microsatellite marker D8S557, indicating heterogeneity with 43% of the families being linked. A multipoint analysis using the markers D8S557 and D8S1835 gave a Z(max) of 3.51, assuming homogeneity. There was significant evidence of heterogeneity with 44.5% of the families being linked. The results indicate that a gene in 8q24 is a common cause of familial congenital hypothyroidism. Since thyroglobulin is essential for thyroid physiology, the gene encoding this protein is the obvious candidate for mutation analysis in the linked families.
先天性甲状腺功能减退症影响1/3000 - 4000名新生儿，据估计，10 - 20%为常染色体隐性遗传模式的家族性病例。以往大多针对个别病例的研究已导致鉴定出多个基因中的突变，表明这是一种基因异质性疾病，但尚未鉴定出主要基因。在本研究中，对23个患有常染色体隐性先天性甲状腺功能减退症但无甲状腺肿大迹象的家族进行了基于人群的样本连锁分析。当在允许异质性的两点分析中使用位于8号染色体q24上靠近甲状腺球蛋白基因的标记时，微卫星标记D8S557获得的Z(max)为4.10，表明异质性，43%的家族呈连锁状态。使用标记D8S557和D8S1835进行的多点分析在假设同质性的情况下得到Z(max)为3.51。有显著证据表明存在异质性，44.5%的家族呈连锁状态。结果表明，8q24上的一个基因是家族性先天性甲状腺功能减退症的常见病因。由于甲状腺球蛋白对甲状腺生理功能至关重要，编码该蛋白的基因是连锁家族中进行突变分析的明显候选基因。
