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Homozygosity mapping of lethal congenital contractural syndrome type 2 (LCCS2) to a 6 cM interval on chromosome 12q13
Author(s) -
Narkis Ginat,
Landau Daniella,
Manor Esther,
Elbedour Khalil,
Tzemach Anna,
Fishelson Ma'ayan,
Geiger Dan,
Ofir Rivka,
Carmi Rivka,
Birk Ohad S.
Publication year - 2004
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.30266
Subject(s) - locus (genetics) , genetics , genetic linkage , gene mapping , biology , disease gene identification , gene , phenotype , chromosomal region , chromosome , exome sequencing
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 ∼6 cM (corresponding to ∼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 ∼6 cM (∼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 θ = 0.01) and D12S1700 (Z max = 9.23 at θ = 0.00). © 2004 Wiley‐Liss, Inc.