Respiratory ciliopathies including non-CF bronchiectasis
Gene: SPEF2Comment on list classification: As reviewed by Steven Cowman, there is sufficient evidence available for this gene to be promoted to green rating in the next GMS update.Created: 11 Dec 2023, 2:36 p.m. | Last Modified: 11 Dec 2023, 2:36 p.m.
Panel Version: 3.9
A report of six male individuals in four families with bi-allelic variants who displayed a PCD-like syndrome of recurrent respiratory infections, bronchiectasis, rhinosinusitis, otitis media and infertility. All had situs solitus. Three individuals in two families showed low nasal nitric oxide levels. Affected individuals displayed abnormal sperm flagella structure on EM; the respiratory cilia in one affected patient were found to be normal on EM but IF found absent SPEF2 protein in contrast to normal individuals.
A report of a single case in a female with chronic sinusitis, bronchiectasis and situs solitus and low nasal nitric oxide. She was found to be homozygous for the c.1860_1861insCT variant. HSVM found mildly reduced ciliary beat frequency and coordination but EM was again normal, IF found absent SPEF2 protein expression in the cilia.
A study of 189 individuals with suspected PCD used IF to screen for the absence of SPEF2 protein in respiratory cilia. In 41 individuals expression was absent, genetic analysis was performed on 39 of whom one was found to be homozygous for the SPEF2 variant c.1693C>T; p.Arg547Ter (an additional 15 had variants in HYDIN). This individual had chronic sinusitis, bronchiectasis and situs solitus. Nasal nitric oxide levels were low and some abnormalities were seen on HSVM, structure on EM was normal.Created: 23 Nov 2023, 12:48 p.m. | Last Modified: 23 Nov 2023, 12:48 p.m.
Panel Version: 3.3
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Primary ciliary dyskinesia
Publications
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM. As respiratory phenotype is not in all affected individuals, this gene has been given an Amber rating.Created: 2 Dec 2020, 3:15 p.m. | Last Modified: 2 Dec 2020, 3:15 p.m.
Panel Version: 1.41
4 families reported with bi-allelic variants and sperm morphological abnormalities plus recurrent sinopulmonary infections and bronchiectasis, consistent with a PCD-like phenotype. Morphological abnormalities of the respiratory cilia were not observed. Mouse model recapitulated the infertility phenotype but also had hydrocephalus and sinusitis, again arguing for broader impact on ciliary function. Note other reports of individuals with bi-allelic variants and no respiratory phenotype reported. Given respiratory phenotype is milder and currently it is unclear in what proportion of individuals it is present, suggest Amber rating on this panel for now.
Sources: Expert listCreated: 25 May 2020, 7:37 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spermatogenic failure 43, MIM#618751; Primary ciliary dyskinesia-like phenotype
Publications
Tag Q4_23_promote_green tag was added to gene: SPEF2. Tag Q4_23_NHS_review tag was added to gene: SPEF2.
Gene: spef2 has been classified as Amber List (Moderate Evidence).
Gene: spef2 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SPEF2 were changed from Spermatogenic failure 43, MIM#618751; Primary ciliary dyskinesia-like phenotype to Spermatogenic failure 43, OMIM:618751, MONDO:0032898; Primary ciliary dyskinesia-like phenotype
gene: SPEF2 was added gene: SPEF2 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: Expert list Mode of inheritance for gene: SPEF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPEF2 were set to 31151990; 31278745; 31048344; 31942643 Phenotypes for gene: SPEF2 were set to Spermatogenic failure 43, MIM#618751; Primary ciliary dyskinesia-like phenotype Review for gene: SPEF2 was set to AMBER