Bardet-Biedl Syndrome 20

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

MKS1, BBS10, SDCCAG8, LZTFL1, BBIP1, CEP290, ARL6, IFT27, BBS2, MKKS, BBS4, BBS1, TTC8, ALMS1, IFT172, C8orf37, NPHP1, TMEM67, TBC1D32, BBS7, TRIM32, BBS9, BBS5, BBS12, TRAPPC3, ASTN2, PIGX, CEP19, ZDHHC24, CCDC28B, LEP, GLIS2, RTEL1, PLLP, PYY3, SULT1A4, PEG13, AZIN1, STOML3, RIN2, MAGEL2, CBLL2, MARVELD2, MYO3B, INPP5E, USP35, MUL1, WDPCP, IFT74, CEP131, SCAPER, INVS, NPY2R, NPY, NMB, NDN, MYO9A, MYO7A, RAB8A, KIFC3, KIF2A, INSR, IL18, GPT, GFAP, ERG, CCT, TNFRSF11B, PRKN, PCM1, ADIPOQ, CEP164, STUB1, FEM1B, RAPGEF5, IQCB1, FEZ1, TRPV1, PDE6B, VEGFA, SULT1A3, RHO, RFX1, RCVRN, PECAM1, SLX1A-SULT1A3

Drugs

Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins, Leuprolide acetate ( LUPRON INJECTION )

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A number sign (#) is used with this entry because of evidence that Bardet-Biedl syndrome-20 (BBS20) is caused by compound heterozygous mutation in the IFT74 gene (608040) on chromosome 9p21. One such patient has been reported.

Description

BBS20 is an autosomal recessive ciliopathy described in a single patient and characterized by retinitis pigmentosa, obesity, polydactyly, hypogonadism, and intellectual disability (Lindstrand et al., 2016).

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

Clinical Features

Lindstrand et al. (2016) reported a 36-year-old man (AR672-04) with BBS. The patient had obesity, polydactyly, hypogonadism, intellectual disability, microcephaly, and retinitis pigmentosa.

Inheritance

The transmission pattern of BBS20 in the family reported by Lindstrand et al. (2016) was consistent with autosomal recessive inheritance.

Molecular Genetics

In a patient with BBS20, Lindstrand et al. (2016) identified compound heterozygous mutations in the IFT74 gene (608040.0001-608040.0002). One mutation was a splice site mutation and the other was an intragenic deletion, and the mutations segregated with the disorder in the family. Analysis of the position of the splice site mutation and the deletion predicted that the patient would have ablated function of only the long isoform of IFT74. Short IFT74 isoforms could partially rescue the phenotype of morpholino knockdown of the ift74 gene in zebrafish, suggesting that the patient was hypomorphic for IFT74 function. The patient was 1 of 92 probands with BBS who were screened for copy number variants in candidate genes. Another BBS patient (AR634-03) with biallelic mutations in the BBS7 gene (607590) carried a heterozygous missense variant in the IFT74 gene (V579M) suggesting oligogenic inheritance. The V579M variant was found in 682 of 120,714 alleles in the ExAC database; functional studies of this variant were not performed.

Animal Model

Lindstrand et al. (2016) found that morpholino knockdown of the ift74 gene and CRISPR/CASP9 genome editing of the ift74 locus in zebrafish resulted in significant gastrulation defects and renal abnormalities consistent with a ciliopathy. The phenotype could be rescued by wildtype IFT74.