Rare multisystem ciliopathy disorders
Gene: PIBF1
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
Comment when marking as ready: Low evidenceCreated: 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
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 relevanceCreated: 5 Jul 2016, 3:41 p.m.
Phenotypes
Joubert syndrome
Publications
Publications for gene: PIBF1 were set to 26167768
Gene: pibf1 has been classified as Green List (High Evidence).
Tag for-review was removed from gene: PIBF1.
Tag for-review tag was added to gene: PIBF1.
Promoted to version 1 by Alice Gardham on 26th January 2017
This gene has been classified as Red List (Low Evidence).
PIBF1 was created by ellenmcdonagh
PIBF1 was added to Rare multisystem ciliopathy disorderspanel. Sources: Expert Review,Literature,Research