Bardet-Biedl Syndrome 16

A number sign (#) is used with this entry because Bardet-Biedl syndrome-16 (BBS16) is caused by homozygous or compound heterozygous mutations in the SDCCAG8 gene (613524) on chromosome 1q43. Mutations in the SDCCAG8 gene can also result in Senior-Loken syndrome-7 (613615), an autosomal recessive ciliopathy.

Description

BBS16 is an autosomal recessive ciliopathy characterized by retinal degeneration, obesity, renal disease, and cognitive impairment. Although polydactyly is considered a primary feature of BBS overall, it has not been reported in any BBS16 patient (Billingsley et al., 2012).

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

Clinical Features

Billingsley et al. (2012) studied 2 female sibs of East Indian descent with BBS. Both subjects, aged 16 and 13 year, respectively, developed end-stage renal disease that required transplantation at 11 and 9 years of age, respectively. Both had obesity, short stature, and mild cognitive impairment. The younger patient had nonalcoholic fatty liver disease. This patient also had trace mitral and tricuspid regurgitation. Visual acuity and central fields were preserved in the teenage years in both patients. Optical coherence tomography showed preservation of the retinal lamination at the fovea; fundus autofluorescence demonstrated a perifoveal ring of hyperfluorescence consistent with retinitis pigmentosa. Full-field ERG showed rod function to be more severely affected than cone function in both cases. Polydactyly was not present.

Schaefer et al. (2010) clinically characterized the patients reported by Otto et al. (2010) and described a previously unreported patient. The 2 consanguineous families studied by Otto et al. (2010) were a Gypsy and a French family, respectively. The phenotype in all families was characterized by obesity, chronic renal failure, cone-rod dystrophy, and developmental delay. Also present were conductive hearing loss/recurrent otitis, respiratory infection, and asthma. Polydactyly was not present in any affected individual.

Molecular Genetics

Otto et al. (2010) carried out an independent homozygosity mapping study on 22 consanguineous families diagnosed with Bardet-Biedl syndrome in whom no mutation had been detected in any of the 12 BBS genes known at that time. They identified homozygosity for mutation in the SDCCAG8 gene in 2 families (613524.0004, 613524.0005). Sequencing of SDCCAG8 in 96 unrelated individuals identified 2 further families in which compound heterozygous loss-of-function mutations seemed to be sufficient to cause the disorder (613524.0006, 613524.0007). Two unique heterozygous alleles were found in 2 additional families.

In 2 sibs of East Indian descent with BBS, Billingsley et al. (2012) identified the same compound heterozygous truncating mutations in the SDCCAG8 gene that had been identified by Otto et al. (2010). Billingsley et al. (2012) referred to the changes observed at the protein level as Thr482LysfsTer12 and Asp543AlsfsTer24. The mutations segregated with the disorder in the family and were not found in 69 matched control individuals. Functional studies of the variants were not performed.