Bardet-Biedl Syndrome 10

A number sign (#) is used with this entry because Bardet-Biedl syndrome-10 (BBS10) is caused by homozygous or compound heterozygous mutation in the BBS10 gene (610148) on chromosome 12q21.

Description

BBS10 is characterized by progressive retinal dystrophy, obesity, polydactyly, cognitive impairment, and renal dysplasia (Stoetzel et al., 2006). BBS10 represents a major locus for BBS, with mutations in the BBS10 gene accounting for approximately 20% of BBS patients (Stoetzel et al., 2006; Zaghloul and Katsanis, 2009).

For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).

Clinical Features

In 6 patients with molecularly confirmed BBS, including 3 patients with BBS10, Scheidecker et al. (2015) found a cone-rod pattern of dysfunction. Macular dystrophy was present in all patients, usually with central hypofluorescence surrounded by a continuous hyperfluorescent ring on fundus autofluorescence imaging. Optical coherence tomography confirmed loss of outer retinal structure within the atrophic areas.

Molecular Genetics

Stoetzel et al. (2006) identified mutations in the putative chaperonin gene BBS10 in 21% (65/311) of an unselected cohort of BBS families of various ethnic origins, including some families with mutations in other BBS genes, consistent with oligogenic inheritance. They found a total of 118 mutated alleles, among which 53 families segregated 2 mutations consonant with the clinical phenotype. A single-nucleotide insertion (610148.0001) accounted for 54 mutant alleles (46%). Stoetzel et al. (2006) concluded that BBS10 is a major BBS gene, mutated as frequently as BBS1 (209901).

In the only affected individual from a sibship within a large consanguineous Lebanese kindred with Bardet-Biedl syndrome reported by Stoetzel et al. (2006), Laurier et al. (2006) found compound heterozygosity for the S311A mutation (610148.0004) and a V11G mutation (610148.0005) in the C12ORF58 gene. Affected individuals from 3 other sibships in this kindred were homozygous for the S311A mutation.

Putoux et al. (2010) identified homozygous or compound heterozygous BBS10 mutations in 5 of 21 patients with polydactyly and antenatal onset of severe renal cystic anomalies, without the biliary or hepatic abnormalities characteristic of Meckel syndrome (MKS; 249000). The most common mutation was the 1-bp duplication (271dupT) identified by Stoetzel et al. (2006), found on 6 of 10 mutant alleles. Four of the patients were fetuses between ages 21 and 26 weeks' gestation, and the fifth was a 20-year-old woman with BBS who was found to have hyperechogenic kidneys and polydactyly on antenatal ultrasound. The 20-year-old woman also carried a heterozygous truncating mutation in the BBS6 gene (604896). Putoux et al. (2010) noted that the diagnosis of severe lethal BBS is suggested in utero by the findings of severe cystic kidneys and polydactyly without biliary dysgenesis or brain anomalies, and concluded that mutations in the BBS10 gene may account for a high percentage of such cases.

Using homozygosity mapping, Harville et al. (2010) identified 17 causative homozygous mutations in 20 families from a worldwide cohort of 45 BBS families. One of these mutations occurred in the BBS10 gene.

Population Genetics

Stoetzel et al. (2006) found that the BBS10 gene was mutated in about 20% of an unselected cohort of BBS families of various ethnic origins. Notably, they found a similar frequency of mutations among families of Middle Eastern ancestry as among those of European ancestry. Twelve of 65 (18%) families with BBS10 mutations also had mutations or recognized variants at another BBS locus, indicative of a potential epistatic interaction.