Rare multisystem ciliopathy disorders

Gene: MKS1

Comment on list classification: Gene is green on the Bardet-Biedl Syndrome panel (version 1.53).

Created: 4 Aug 2016, 3:54 p.m.

Green List (high evidence)

Along with MKS3 (TMEM67), one of the most common causes of Meckel-Gruber syndrome (MKS). Accounts for around 7% of all cases, and 70% of Finnish cases.

Mutations often affect splicing. Common Finn major mutation, 29bp deletion in intron 15 4bp from splice acceptor site. Predicted to affect splicing and cause frame-shifts which lead to nonsense-mediated decay and are therefore functional nulls.

Inherited in autosomal recessive homozygous and compound heterozygous pattern.

Skeletal involvement (the 'campomelic form') more common in MKS caused by MKS1 mutations. MKS1 mutations almost always associated with polydactyly and shortening and bowing of the long bones.

Single heterozygous mutations found in 5 BBS families, accompanied by homozygous mutations in BBS1 or BBS10. In these cases, MKS1 mutation considered a modifier. In two BBS families, compound heterozygous mutations have been found in MKS1 with no mutations in other known BBS genes. The mutations are; pC492W missense and F371del in one family and; Y461C and R534Q in another family; these are suggested to be hypomorphic mutations, suggested to cause milder BBS than null mutations causing MKS.

Created: 5 Jul 2016, 3:10 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Meckel-Gruber syndrome; Meckel syndrome; Bardet-Biedl syndrome; occipital encephalocele; polycystic kidneys; renal fibrosis; polydactyly

Publications

• PMID: 16415886
• PMID: 17437276

Mode of pathogenicity
Other

Green List (high evidence)

On current diagnostic panel and positive families within patient cohort. Evidence from literature.

Created: 15 Mar 2016, 3:37 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome; Meckel-Gruber syndrome

Publications

• 24886560
• 26490104

Variants in this GENE are reported as part of current diagnostic practice

Comment on list classification: Meckel syndrome

Created: 17 Dec 2015, 2:39 p.m.

Red List (low evidence)

Mutations in this gene more commonly cause Meckel syndrome, only a single BBS case reported.

Created: 14 Oct 2015, 12:15 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
249000

Publications

• 18327255
• 16415886