Respiratory ciliopathies including non-CF bronchiectasis
Gene: OFD1
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
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
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 givenCreated: 5 Dec 2018, 1:54 p.m.
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
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
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
Tag for-review was removed from gene: OFD1.
Source Expert Review Green was added to OFD1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mode of inheritance for gene: OFD1 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Tag for-review tag was added to gene: OFD1.
Publications for gene: OFD1 were set to 31366608; 32276433; 31373179; 16783569
Publications for gene: OFD1 were set to
Phenotypes for gene: OFD1 were changed from Ciliopathies; Primary ciliary dyskinesia to Ciliopathies; Primary ciliary dyskinesia; Simpson-Golabi-Behmel syndrome, type 2, OMIM:300209, MONDO:0010265
Phenotypes for gene: OFD1 were changed from Ciliopathies to Ciliopathies; Primary ciliary dyskinesia
Added phenotypes Ciliopathies for gene: OFD1
Source Expert Review Amber was added to OFD1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
gene: OFD1 was added gene: OFD1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS Mode of inheritance for gene: OFD1 was set to