A proposed new contiguous gene syndrome on 8q consists of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, a dominant form of hydrocephalus and trapeze aplasia; implications for the mapping of the BOR gene

Abstract

The analysis of a de novo 8q12.2-q21.2 deletion led to the identification of a proposed previously undescribed contiguous gene syndrome consisting of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, hydrocephalus and trapeze aplasia. This is the first reported localization of the genes responsible for Duane syndrome and this dominant form of hydrocephalus. In contrast, we report a new localization for the gene responsible for BOR syndrome which is more telomeric to an initial placement. Linkage analysis of affected families consistently mapped the gene responsible for BOR and Branchio-Oto (BO) syndromes to within the deletion. Using new algorithms, a YAC contig was constructed and used to localize the breakpoint of another chromosomal rearrangement associated with BO syndrome to a 500 kb interval within the deletion. The 8q12.2-q21.2 deletion suggests that reduced dosage of the relevant genes is sufficient to cause Duane syndrome, BOR syndrome and this dominant form of hydrocephalus.

Narrowing the Duane syndrome critical region at chromosome 8q13 down to 40 kb

“…In conclusion, the association of Duane syndrome with a 8q13 rearrangement in the patient described here and in two previously reported cases 5,6 strongly supports the location of a gene for Duane syndrome at 8q13. In this study the 8q Duane syndrome gene interval has been narrowed down to a 40 kb interval between markers SHGC37325 and WI4901.…”

“…4 Furthermore, chromosome anomalies have been observed in some Duane patients and an 8q12-13 contiguous gene syndrome including Duane syndrome has been proposed. 5 Recently, a comparison of boundaries in two patients with 8q13 deletions 5,6 allowed us to narrow down the Duane syndrome smallest region of overlap (SRO) to a < 3 cM interval between D8S533 and D8S1767. 6 In this study we report a Duane syndrome patient carrying a constitutional translocation involving region 8q13.…”

Detection of an insertion deletion of region 8q13-q21.2 in a patient with Duane syndrome: implications for mapping and cloning a Duane gene

“…In fact a few atypical cases of Duane syndrome have been described in association with deafness, renal defects, muscular, and skeletal anomalies 4-7 and chromosome imbalances. [7][8][9][10] In particular a contiguous gene syndrome consisting of Duane syndrome, branchio-oto-renal syndrome (BOR), hydrocephalus and trapeze aplasia was found in a patient with 8q12.2-q21.2 deletion. 7 We report on an insertion deletion of chromosome 8q13-q21.2 in a patient presenting with Duane syndrome type I, severe mental retardation, and minor limbs abnormalities.…”

“…[7][8][9][10] In particular a contiguous gene syndrome consisting of Duane syndrome, branchio-oto-renal syndrome (BOR), hydrocephalus and trapeze aplasia was found in a patient with 8q12.2-q21.2 deletion. 7 We report on an insertion deletion of chromosome 8q13-q21.2 in a patient presenting with Duane syndrome type I, severe mental retardation, and minor limbs abnormalities. Molecular studies were carried out in order to analyse and map this Duane syndrome containing region.…”

Congenital innervation dysgenesis syndrome (CID)/congenital cranial dysinnervation disorders (CCDDs)

“…61 The DURS1 locus is assumed to reflect disruption of a gene for isolated DRS and is defined by cytogenetic abnormalities of 8q12.2-8q21.2. [62][63][64] The chromosome 8 break point was found to occur between exons 1 and 2 of a carboxypeptidase gene, CPA6 (CPAH), which is hypothesised to have a role in peptide processing in the brain. 64 …”