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Refining the region of branchio-oto-renal syndrome and defining the flanking markers on chromosome 8q by genetic mapping.

ABSTRACT: Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder associated with external-, middle-, and inner-ear malformations, branchial cleft sinuses, cervical fistulas, mixed hearing loss, and renal anomalies. The gene for BOR was mapped to the long arm of chromosome 8q. Several polymorphic dinucleotide repeat markers were investigated for linkage in two large BOR families, and the region of localization was refined. Two-point linkage analysis yielded the maximum lod scores of 7.44 at theta = .03 and 6.71 at theta = .04, with markers D8S279 and D8S260, respectively. A multipoint analysis was carried out to position the BOR gene with a defined region using markers D8S165, D8S285, PENK, D8S166, D8S260, D8S279, D8S164, D8S286, D8S84, D8S275, D8S167, D8S273, and D8S271. Haplotype analysis of recombination events at these polymorphic loci was also performed in multigeneration BOR kindreds. The linkage analysis and analysis of recombination events identified markers that clearly flank the BOR locus. The order was determined to be D8S260-BOR-D8S279 at odds > 10(3):1 over the other possible orders. This flanking markers provide a resource for high-resolution mapping toward cloning and characterizing the BOR gene.

SUBMITTER: Kumar S

PROVIDER: S-EPMC1918457 | biostudies-other | 1994 Dec

REPOSITORIES: biostudies-other

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Refining the region of branchio-oto-renal syndrome and defining the flanking markers on chromosome 8q by genetic mapping.

Kumar S S Kimberling W J WJ Connolly C J CJ Tinley S S Marres H A HA Cremers C W CW

American journal of human genetics 19941201 6

Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder associated with external-, middle-, and inner-ear malformations, branchial cleft sinuses, cervical fistulas, mixed hearing loss, and renal anomalies. The gene for BOR was mapped to the long arm of chromosome 8q. Several polymorphic dinucleotide repeat markers were investigated for linkage in two large BOR families, and the region of localization was refined. Two-point linkage analysis yielded the maximum lod scores of 7.44 at th ...[more]

PMID: 7977379

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Project description:Branchio-oto syndrome (BOS)/branchio-oto-renal syndrome (BORS) is a kind of autosomal dominant heterogeneous disorder. These diseases are mainly characterized by hearing impairment and abnormal phenotype of ears, accompanied by renal malformation and branchial cleft anomalies including cyst or fistula, with an incidence of 1/40 000 in human population. Otic anormalies are one of the most obvious clinical manifestations of BOS/BORS, including deformities of external, middle, inner ears and hearing loss with conductive, sensorineural or mix, ranging from mild to profound loss. Temporal bone imaging could assist in the diagnosis of middle ear and inner ear malformations for clinicians. Multiple methods including direct sequencing combined with next generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), or array-based comparative genomic hybridization (aCGH) can effectively screen and identify pathogenic genes and/or variation types of BOS/BORS. About 40% of patients with BOS/BORS carry aberrations of EYA1 gene which is the most important cause of BOS/BORS. A total of 240 kinds of pathogenic variations of EYA1 have been reported in different populations so far, including frameshift, nonsense, missense, aberrant splicing, deletion and complex rearrangements. Human Endogenous Retroviral sequences (HERVs) may play an important role in mediating EYA1 chromosomal fragment deletion mutations caused by non-allelic homologous recombination. EYA1 encodes a phosphatase-transactivator cooperated with transcription factors of SIX1, participates in cranial sensory neurogenesis and development of branchial arch-derived organs, then regulates the morphological and functional differentiation of the outer ear, middle ear and inner ear toward normal tissues. In addition, pathogenic mutations of SIX1 and SIX5 genes can also cause BOS/BORS. Variations of these genes mentioned above may cause disease by destroying the bindings between SIX1-EYA1, SIX5-EYA1 or SIX1-DNA. However, the role of SIX5 gene in the pathogenesis of BORS needs further verification.

Dataset Information

Refining the region of branchio-oto-renal syndrome and defining the flanking markers on chromosome 8q by genetic mapping.

Publications

Refining the region of branchio-oto-renal syndrome and defining the flanking markers on chromosome 8q by genetic mapping.

Similar Datasets

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