title: Assignment of the mulibrey nanism gene to 17q by linkage and linkage-disequilibrium analysis.
abstract: 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.
authors.affiliation: Department of Medical Genetics, University of Helsinki, Folkhälsan Institute of Genetics, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Avela
authors.forename: M
authors.initials: M
authors.lastname: Lipsanen-Nyman
authors.forename: J
authors.initials: J
authors.lastname: Perheentupa
authors.forename: C
authors.initials: C
authors.lastname: Wallgren-Pettersson
authors.forename: S
authors.initials: S
authors.lastname: Marchand
authors.forename: S
authors.initials: S
authors.lastname: Fauré
authors.forename: P
authors.initials: P
authors.lastname: Sistonen
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: A E
authors.initials: AE
authors.lastname: Lehesjoki
mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology / Q000235:genetics*; D001921:Brain / Q000002:abnormalities; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004392:Dwarfism / Q000453:epidemiology / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D005808:Genes, Recessive; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008099:Liver / Q000002:abnormalities; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009132:Muscles / Q000002:abnormalities; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic
chemical_list: D005819:Genetic Markers; D018398:Homeodomain Proteins