Avela K, Lipsanen-Nyman M, Perheentupa J, Wallgren-Pettersson C, Marchand S, Fauré S, Sistonen P, de la Chapelle A, Lehesjoki A E
Department of Medical Genetics, University of Helsinki, Folkhälsan Institute of Genetics, Finland.
Am J Hum Genet. 1997 Apr;60(4):896-902.
Mulibrey nanism (MUL) is an autosomal recessive disorder with unknown basic metabolic defect. It is characterized by growth failure of prenatal onset, characteristic dysmorphic features, constrictive pericardium, hepatomegaly as a consequence of constrictive pericardium, yellowish dots in the ocular fundi, and J-shaped sella turcica. Hypoplasia of various endocrine glands, causing hormone deficiencies, is common. Here we report the assignment of the MUL gene, by linkage analysis in Finnish families, to a 7-cM region flanked by D17S1799 and D17S948 on chromosome 17q. Multipoint linkage analysis gave a maximum LOD score of 5.01 at loci D17S1606-D17S1853 and at D17S1604. The estimate of the critical MUL region was further narrowed to within approximately 250 kb of marker D17S1853 by linkage disequilibrium analysis. Positional candidate genes that belong to the growth hormone and homeobox B gene clusters were excluded. These data confirm the autosomal recessive inheritance of MUL and allow highly focused attempts to clone the gene.
穆利布雷侏儒症（MUL）是一种常染色体隐性疾病，其基本代谢缺陷不明。其特征为产前起病的生长发育迟缓、特征性的畸形面容、缩窄性心包炎、因缩窄性心包炎导致的肝肿大、眼底黄斑以及J形蝶鞍。各种内分泌腺发育不全导致激素缺乏很常见。在此，我们通过对芬兰家族进行连锁分析，报告了MUL基因定位于17号染色体长臂上D17S1799和D17S948之间7厘摩的区域。多点连锁分析在D17S1606 - D17S1853位点和D17S并排除了属于生长激素和同源框B基因簇的位置候选基因。这些数据证实了MUL的常染色体隐性遗传，并有助于高度集中地尝试克隆该基因。 1604位点获得了最高对数优势分数5.01。通过连锁不平衡分析，关键的MUL区域估计进一步缩小至标记D17S1853约250 kb范围内。属于生长激素和同源框B基因簇的位置候选基因被排除。这些数据证实了MUL的常染色体隐性遗传，并有助于高度集中地尝试克隆该基因。
