Rare multisystem ciliopathy disorders

Gene: PIBF1

Green List (high evidence)

Comment on list classification: With the addition of the two recent reports, there are now at least 7 total families (4 with same founder variant) with Joubert syndrome associated with biallelic variants in this gene.

Created: 18 Aug 2020, 4:59 p.m. | Last Modified: 18 Aug 2020, 4:59 p.m.

Panel Version: 1.128

Associated with Joubert syndrome in OMIM, and a confirmed gene in G2P.

PMID: 26167768 (2015) - Homozygous founder variant (c.1910A>C, p.Asp637Ala) identified in six individuals from four Hutterite families affected with Joubert syndrome. Analysis of an additional 643 Joubert families revealed 7 families with heterozygous truncating PIBF1 variants - unclear whether these were monoallelic or compound heterozygous (one comp het case, UW155-3, included in supplementary data).

PMID: 29695797 (2018) - Biallelic in-frame insertion (p.Gln394_Leu395ins12) of 36-bp in exon 9 of PIBF1 was identified in a two-year-old girl with Joubert syndrome. The variant segregated with the phenotype, however no further functional validation was performed.

PMID: 30858804 (2019) - Compound heterozygous variants (p.Y503C and p.Q485*) identified in a patient with Joubert syndrome. Functional data using the frog Xenopus as an animal model, demonstrates defects in cilia functions.

Created: 18 Aug 2020, 4:55 p.m. | Last Modified: 18 Aug 2020, 4:55 p.m.

Panel Version: 1.127

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 33, 617767

Publications

• 26167768
• 29695797
• 30858804

Comment when marking as ready: Low evidence

Created: 25 Jan 2017, 1:56 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome; vermis hypoplasia; thick superior cerebellar peduncles; superior cerebellar dysplasia; ataxia; developmental delay

Publications

• 26167768

Homozygous c.1910A>C p.Asp637Ala missense mutation in 4 Hutterite Joubert families. Hypomorphic mutation rather than complete null. This allele didn't rescue loss of cilia after Pibf1 siRNA knockdown in cell cultures, but expression of wild-type PIBF1 did. 7 Joubert families with heterozygous PIBF1 mutations, unknown clinical relevance

Created: 5 Jul 2016, 3:41 p.m.

Phenotypes
Joubert syndrome

Publications

• PMID: 26167768