DO: 0081009;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2p23.3 | Bardet-Biedl syndrome 20 | 619471 | Autosomal recessive | 3 | IFT172 | 607386 |
A number sign (#) is used with this entry because of evidence that Bardet-Biedl syndrome-20 (BBS20) is caused by homozygous or compound heterozygous mutation in the IFT172 gene (607386) on chromosome 2p23.
Bardet-Biedl syndrome-20 (BBS20), a rare autosomal recessive disorder associated with ciliary dysfunction, is characterized by rod-cone dystrophy, postaxial polydactyly, truncal obesity, renal anomalies, and learning disability, as well as hypogonadism in males and genital abnormalities in females (Saida et al., 2014).
For a general phenotypic description and discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
A form of Bardet-Biedl syndrome caused by mutation in the IFT74 gene (608040), formerly designated BBS20, is now designated BBS22 (617119). The numbering has been changed in OMIM to avoid future confusion in the literature.
Saida et al. (2014) described a 9-year-old Japanese girl who presented with proteinuria and renal dysfunction. She was born with postaxial polydactyly that was resected soon after birth as well as an atrial septal defect that was repaired at age 1 year. Other medical problems included exudative otitis media and hearing impairment, strabismus, hyperopia, astigmatism, and night blindness. She also had obesity, with a BMI of 23, and borderline intellectual impairment, with an IQ of 76. Renal biopsy showed obsolescence and hyalinization of glomerula as well as interstitial fibrosis without tubule involvement. Rod-cone dystrophy was evident on electroretinography, with severely reduced responses bilaterally, and Goldman perimetry revealed visual field constriction. Based on these findings, the patient was diagnosed with BBS. She also had papilledema with tortuous retinal vessels and elevated intracranial pressure. She received a renal transplant from her mother at age 11. The authors stated that this was the first report of a BBS patient with intracranial hypertension.
Bujakowska et al. (2015) reported 2 sisters (family 1), aged 15 and 22 years, who had retinitis pigmentosa (RP) as well as systemic features suggesting a Bardet-Biedl-like ciliopathy. Onset of night blindness occurred in the first decade of life. Both were obese and had a history of delayed speech development and elevated liver transaminases. The younger sister also exhibited bilateral postaxial cutaneous polydactyly, hypercholesterolemia, and pancreatitis. Neither sib had skeletal anomalies.
Schaefer et al. (2016) studied 2 brothers with Bardet-Biedl syndrome, born of consanguineous parents of Melanesian ancestry. The first brother (IV.3) was overweight at age 18 years and had RP, learning difficulties, and asthma. His 13-year-old brother (IV.5) was born with postaxial polydactyly of the right hand and bilateral preaxial polydactyly of the feet, and had delayed development and obesity. Skeletal x-rays confirmed the polydactyly, with duplication of the metatarsus and phalanges without other abnormalities. Hypogonadism with micropenis and bilateral cryptorchidism was diagnosed at age 2 years, and RP was diagnosed at age 3. Brain and renal imaging was normal in both brothers.
The transmission pattern of BBS20 in the family reported by Bujakowska et al. (2015) was consistent with autosomal recessive inheritance.
In 2 sisters (family 1) with RP and obesity, who were negative for mutation in 12 BBS-associated genes, Bujakowska et al. (2015) performed whole-exome sequencing and identified compound heterozygosity for a missense mutation (H1567Q; 607386.0013) and a splice site mutation (607386.0014) in the IFT172 gene. Their unaffected parents were each heterozygous for one of the mutations.
By whole-exome sequencing in 2 brothers (IV.3 and IV.5) with BBS, who were born of consanguineous parents of Melanesian origin, Schaefer et al. (2016) identified homozygosity for a splicing mutation in the IFT172 gene (607386.0018). Sanger sequencing confirmed the mutation and its segregation with disease in the family.
In a 9-year-old Japanese girl (patient 2) with BBS, originally reported by Saida et al. (2014), Hirano et al. (2020) performed exome sequencing and identified compound heterozygosity for 2 missense mutations in the IFT172 gene (L493R, 607386.0019 and H719Y, 607386.0020). The mutations were confirmed by Sanger sequencing, and her unaffected parents were each heterozygous for one of the mutations. Saida et al. (2014) had excluded mutation in 14 known BBS-associated genes in this patient.
Bujakowska, K. M., Zhang, Q., Siemiatkowska, A. M., Liu, Q., Place, E., Falk, M. J., Consugar, M., Lancelot, M-E., Antonio, A., Lonjou, C., Carpentier, W., Mohand-Said, S., and 10 others. Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome. Hum. Molec. Genet. 24: 230-242, 2015. [PubMed: 25168386] [Full Text: https://doi.org/10.1093/hmg/ddu441]
Hirano, M., Satake, W., Moriyama, N., Saida, K., Okamoto, N., Cha, P.-C., Suzuki, Y., Kusunoki, S., Toda, T. Bardet-Biedl syndrome and related disorders in Japan. J. Hum. Genet. 65: 847-853, 2020. [PubMed: 32451492] [Full Text: https://doi.org/10.1038/s10038-020-0778-y]
Saida, K., Inaba, Y., Hirano, M., Satake, W., Toda, T., Suzuki, Y., Sudo, A., Noda, S., Hidaka, Y., Hirabayashi, K., Imai, H., Kurokawa, T., Koike, K. A case of Bardet-Biedl syndrome complicated with intracranial hypertension in a Japanese child. Brain Dev. 36: 721-724, 2014. [PubMed: 24290075] [Full Text: https://doi.org/10.1016/j.braindev.2013.10.013]
Schaefer, E., Stoetzel, C., Scheidecker, S., Geoffroy, V., Prasad, M. K., Redin, C., Missotte, I., Lacombe, D., Mandel, J.-L., Muller, J., Dollfus, H. Identification of a novel mutation confirms the implication of IFT172 (BBS20) in Bardet-Biedl syndrome. J. Hum. Genet. 61: 447-450, 2016. [PubMed: 26763875] [Full Text: https://doi.org/10.1038/jhg.2015.162]