title: Homozygosity mapping of lethal congenital contractural syndrome type 2 (LCCS2) to a 6 cM interval on chromosome 12q13.
abstract: We have recently described a novel autosomal recessive disorder, lethal congenital contractural syndrome type 2 (LCCS2) (OMIM 607598), in a large Israeli Bedouin kindred. The phenotype, which is lethal in the neonatal period, is distinguished by the presence of a markedly distended urinary bladder. Association of LCCS2 to the known loci associated with arthogryposis was excluded. In the present study, we set out to determine the genetic locus harboring the gene defective in this disease. We performed genome-wide linkage analysis, demonstrating linkage to a approximately 6 cM (corresponding to approximately 7.2 Mb) homozygosity region on chromosome 12q13 between markers D12S1604 and D12S83. Based on recombination events, the interval harboring the disease-associated locus was further narrowed to a region spanning approximately 6 cM ( approximately 6.4 Mb) between D12S325 and D12S1072. Linkage of LCCS2 to that locus was established, with two significant maximum peaks at markers D12S1604 (Z(max) = 10.56 at theta = 0.01) and D12S1700 (Z(max) = 9.23 at theta = 0.00).
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ginat
authors.initials: G
authors.lastname: Narkis
authors.forename: Daniella
authors.initials: D
authors.lastname: Landau
authors.forename: Esther
authors.initials: E
authors.lastname: Manor
authors.forename: Khalil
authors.initials: K
authors.lastname: Elbedour
authors.forename: Anna
authors.initials: A
authors.lastname: Tzemach
authors.forename: Ma'ayan
authors.initials: M
authors.lastname: Fishelson
authors.forename: Dan
authors.initials: D
authors.lastname: Geiger
authors.forename: Rivka
authors.initials: R
authors.lastname: Ofir
authors.forename: Rivka
authors.initials: R
authors.lastname: Carmi
authors.forename: Ohad S
authors.initials: OS
authors.lastname: Birk
mesh_terms: D002874:Chromosome Mapping / Q000379:methods*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003286:Contracture / Q000151:congenital / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D013577:Syndrome