Respiratory ciliopathies including non-CF bronchiectasis

Gene: OFD1

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 11:15 a.m. | Last Modified: 8 Mar 2022, 11:15 a.m.

Panel Version: 1.55

PMID:16783569 describes an affected family with Simpson-Golabi-Behmel syndrome type 2. Index case is male and have recurrent upper and lower airway defects, IQ = 20 and dysmorphic features. Other affected males in the family had respiratory distress syndrome and recurrent respiratory tract infection and some of them have died from pulmonary insuffiency.

PMID:22548404 describes a case in Japan where affected males had severe respiratory insufficiency, dysmorphic features and eye abnormalities.

PMID:31366608 describes 4 cases with different variants in this gene. Affected males had typical PCD features without severe neurological, skeletal or renal symptoms characteristic for other OFD1-related syndromes. All four patients had sparse cilia. One patient has situs inversus.

PMID:31373179 describes 3 cases with PCD. One patient has situs inversus totalis.

Taken together with there is enough evidence to support a gene-disease association. This gene should be promoted to Green status at the next review.

Created: 1 Dec 2020, 4:03 p.m. | Last Modified: 1 Dec 2020, 4:03 p.m.

Panel Version: 1.13

Publication from 2019: Truncating Mutations in Exons 20 and 21 of OFD1 Can Cause Primary Ciliary Dyskinesia Without Associated Syndromic Symptoms. PMID: 31366608 DOI: 10.1136/jmedgenet-2018-105918 .
A novel hemizygous truncating mutation in OFD1 exon 20 was found by GOSH in a Wessex patient negative for our in-house PCD panel.
Sequencing of these exons could be included in the PCD panel or at least reviewed as part of amber gene data collection.

Created: 3 Jul 2020, 12:02 p.m. | Last Modified: 3 Jul 2020, 12:17 p.m.

Panel Version: 1.7

Green List (high evidence)

The conditions associated with this gene are not primary ciliary dyskinesias. However, note 7 individuals reported with PCD phenotype.

Created: 6 Jul 2020, 9:35 a.m. | Last Modified: 6 Jul 2020, 9:35 a.m.

Panel Version: 1.7

Phenotypes
Primary ciliary dyskinesia

Publications

• 32276433
• 31373179

I don't know

Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: OFD1; Suggested initial gene rating: Amber; Evidence for inclusion: SGBS2 involves recurrent upper respiratory infections; Evidence for exclusion: Only one family with this, also syndromic w/ severe ID etc, unlikely to be referred for non-syndromic PCD panel.; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 5 Dec 2018, 1:54 p.m.

Red List (low evidence)

Phenotype not relevant to isomerism / laterality. Excluded on this basis, rather than causation.

Created: 4 Jul 2017, 7:25 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Orofaciodigital syndrome; Joubert syndrome

Red List (low evidence)

Gene should be deleted - causes a primary ciliopathy;PCD is a motile ciliopathy, likely unrelated at a functional level.

Created: 8 Dec 2015, 5:33 p.m.

Phenotypes
ciliopathies

Red List (low evidence)

OFD1 is published to cause Simpson-Golabi-Behmel syndrome type 2 where patients have neurological symptoms but also have ciliary defects akin to PCD. We have found in UK clinics two families with OFD1 mutations that cause a syndromic form of PCD i.e. cause a primary ciliopathy, but with defects of function of the motile cilia. This is very new data, backing up a growing understanding that motile cilia can cause respiratory disease in primary ciliopathy patients. Therefore, there is decent evidence to list this as a syndromic PCD gene. In my view this is a green gene, that should be held on PCD gene lists.

Created: 8 Dec 2015, 4:25 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Simpson-Golabi-Behmel syndrome, type 2

Publications

• PMID:16783569