Genetic homogeneity, high-resolution mapping, and mutation analysis of the urofacial (Ochoa) syndrome and exclusion of the glutamate oxaloacetate transaminase gene (GOT1) in the critical region as the disease gene.

The urofacial (Ochoa) syndrome (UFS) is a rare autosomal recessive disorder characterized by abnormal facial expression and urinary abnormalities. Previously, we mapped the gene to a genomic interval of approximately 1 cM on chromosome region 10q23-24, using families from Columbia. Here we demonstrate genetic homogeneity of the syndrome through homozygosity mapping in American patients with Irish heritage. We established a physical map and identified novel polymorphic markers in the UFS critical region. Haplotype analysis using the new markers mapped the UFS gene within one YAC clone of 1,410 kb. We also determined the precise location of the gene encoding for glutamate oxaloacetate transaminase (GOT1) within the new UFS critical region and determined its genomic structure. However, mutation analysis excluded GOT1 as a candidate for the UFS gene.

Wang CY ，Huang YQ ，Shi JD ，Marron MP ，Ruan QG ，Hawkins-Lee B ，Ochoa B ，She JX ... -  《american journal of medical genetics》

Construction of a physical and transcript map for a 1-Mb genomic region containing the urofacial (Ochoa) syndrome gene on 10q23-q24 and localization of the disease gene within two overlapping BAC clones (<360 kb).

Urofacial (Ochoa) syndrome is an autosomal recessive disease characterized by distorted facial expression and urinary abnormalities. Previously, we mapped the UFS gene to chromosome 10q23-q24 and narrowed the interval to one YAC clone of 1410 kb. Here, we have constructed a BAC/PAC contig of the 1-Mb region using STS content mapping with 42 BAC/PAC-end sequences, 9 previously reported and 16 newly identified microsatellite markers, and 14 EST markers. A total of 26 polymorphic microsatellite markers were genotyped for 31 UFS patients from Colombia and 2 patients from the United States. Haplotype analyses suggest that the UFS gene is located within two overlapping BAC clones, a region of <360 kb of DNA sequence. We tested 42 EST markers previously mapped to the D10S1709-D10S603 interval against the BAC/PAC contig and identified 11 ESTs located in the 1-Mb region. Four of the 11 ESTs mapped to the 360-kb UFS critical region. Shotgun sequencing of the two BAC clones and BLASTN search of the EST databases revealed 3 other ESTs contained in the UFS critical region. These results will facilitate the cloning and identification of the UFS gene.

Wang CY ，Shi JD ，Huang YQ ，Cruz PE ，Ochoa B ，Hawkins-Lee B ，Davoodi-Semiromi A ，She JX ... -  《GENOMICS》

High resolution mapping and mutation analyses of candidate genes in the urofacial syndrome (UFS) critical region.

The urofacial (Ochoa) syndrome (UFS) characterized by congenital obstructive uropathy and abnormal facial expression is a rare disorder caused by a single recessive disease gene. Our previous studies using homozygosity mapping have located the UFS gene to a genomic interval of approximately 360 kb on chromosome 10q23-10q24. In this study, we have constructed a genomic sequence map covering the entire UFS interval and narrowed the disease interval to a genomic region of 220 kb that harbor the newly identified ACDP1 gene in addition to part of the GOT1 gene which has already been excluded as a candidate for UFS. Extensive search for mutations in the coding region, the 5' and 3' untranslated regions, the promoter region, and the exon/intron junctions failed to identify a pathogenic mutation in UFS patients. Furthermore, our analyses indicated that the same gene on chromosome 10q is responsible for all UFS patients from multiple ethnic groups.

Wang CY ，Davoodi-Semiromi A ，Shi JD ，Yang P ，Huang YQ ，Agundez JA ，Moran JM ，Ochoa B ，Hawkins-Lee B ，She JX ... -  《AMERICAN JOURNAL OF MEDICAL GENETICS PART A》

Expression analysis of 21 transcripts physically anchored within the chromosomal region 10q24.

Nobile C ，Pitzalis S 《GENOMICS》

Genetic homogeneity of the urofacial (Ochoa) syndrome confirmed in a new French family.

The urofacial syndrome (UFS) or Ochoa syndrome has been reported as a rare autosomal recessive disorder comprising a uropathy and facial abnormalities. The gene was mapped on chromosome region 10q23-q24. We report the first European cases of UFS. Haplotype analyses in our French family were compared with those previously described in patients from Columbia and America (literature data). The results are compatible with the same localization of the critical region and favor the hypothesis of genetic homogeneity.

Chauve X ，Missirian C ，Malzac P ，Girardot L ，Guys JM ，Louis C ，Philip N ，Voelckel MA ... -  《american journal of medical genetics》