TY - JOUR
T1 - Autozygosity mapping of Bardet-Biedl syndrome to 12q21.2 and confirmation of FLJ23560 as BBS10
AU - White, Dominic R.A.
AU - Ganesh, Anuradha
AU - Nishimura, Darryl
AU - Rattenberry, Eleanor
AU - Ahmed, Shakeel
AU - Smith, Ursula M.
AU - Pasha, Shanaz
AU - Raeburn, Sandy
AU - Trembath, Richard C.
AU - Rajab, Anna
AU - Macdonald, Fiona
AU - Banin, Eyal
AU - Stone, Edwin M.
AU - Johnson, Colin A.
AU - Sheffield, Val C.
AU - Maher, Eamonn R.
N1 - Funding Information:
We thank the many referring clinicians and the families who participated in our research studies. In addition, we thank C Searby and G Beck for technical assistance. We thank the Medical Research Council and the Wellcome Trust for financial support. This work was also supported by National Institutes of Health grant R01-EY11298 (VCS and EMS, the Carver Endowment for Molecular Ophthalmology (EMS and VCS), and Research to Prevent Blindness (Department of Ophthalmology, University of Iowa). VCS and EMS are investigators of the Howard Hughes Medical Institute.
PY - 2007/2
Y1 - 2007/2
N2 - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by variable obesity, pigmentary retinopathy, polydactyly, mental retardation, hypogonadism and renal failure. In order to identify novel BBS loci we undertook autozygosity mapping studies using high-density SNP microarrays in consanguineous kindreds. We mapped a BBS locus to a 10.1Mb region at 12q15-q21.2 in a large Omani BBS family (peak lod score 8.3 at θ=0.0 for marker D12S1722) that contained the recently described BBS10 locus. Mutation analysis of candidate genes within the target interval, including the BBS10 gene, revealed a homozygous frameshift mutation in FLJ23560 and mutations were also detected in four smaller consanguineous families with regions of autozygosity at 12q21.2. These findings (a) confirm a previous report that FLJ23560 (BBS10) mutations are a significant cause of BBS, and (b) further demonstrate the utility of high-density SNP array mapping in consanguineous families for the mapping and identification of recessive disease genes.
AB - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by variable obesity, pigmentary retinopathy, polydactyly, mental retardation, hypogonadism and renal failure. In order to identify novel BBS loci we undertook autozygosity mapping studies using high-density SNP microarrays in consanguineous kindreds. We mapped a BBS locus to a 10.1Mb region at 12q15-q21.2 in a large Omani BBS family (peak lod score 8.3 at θ=0.0 for marker D12S1722) that contained the recently described BBS10 locus. Mutation analysis of candidate genes within the target interval, including the BBS10 gene, revealed a homozygous frameshift mutation in FLJ23560 and mutations were also detected in four smaller consanguineous families with regions of autozygosity at 12q21.2. These findings (a) confirm a previous report that FLJ23560 (BBS10) mutations are a significant cause of BBS, and (b) further demonstrate the utility of high-density SNP array mapping in consanguineous families for the mapping and identification of recessive disease genes.
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U2 - 10.1038/sj.ejhg.5201736
DO - 10.1038/sj.ejhg.5201736
M3 - Article
C2 - 17106446
AN - SCOPUS:33846309666
VL - 15
SP - 173
EP - 178
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 2
ER -