Fetal anomalies
Gene: NDUFB11
This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.Created: 5 May 2023, 3 p.m. | Last Modified: 5 May 2023, 3 p.m.
Panel Version: 3.8
On 14 panels, inc. fetal anomalies, DDG2P, IEM, severe paediatric disorders. Associated with ?Mitochondrial complex I deficiency, nuclear type 30 (XL), Linear skin defects with multiple congenital anomalies 3 (XLD). In OMIM MC1DN30: Onset at birth. Neonatal death. Prenatal manifestations: IUGR, premature birth. Notes in R21: 09/08/22 Following clinical review, it was agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update. Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.Van Rahden et al. (2015) (PMID: 25772934) reported 2 unrelated girls with linear skin defects of the face and neck at birth, cardiomyopathy, and various other congenital anomalies. One of them had ACC and dilated lateral ventricles on prenatal ultrasound. There was a second affected female pregnancy in the same family with thickened myocardium and pericardial effusion, corpus-callosum dysgenesis, a small cerebellum, and a connection between a lateral ventricle and the cavum septum pellucidum, as well as intrauterine growth retardation (confirmed to have the same variant). The mother was also heterozygous for the variant but unaffacted, with skewed X-inactivation. Also identified on gene agnostic re-analysis of a fetal case tested in the GMS: heterozygous de novo pathogenic variant in a female with ACC, VSD, ventricular hypertrophy, polyhydramnios. Conclusion: due to be upgraded to green on next panel update.Created: 5 May 2023, 3 p.m. | Last Modified: 5 May 2023, 3 p.m.
Panel Version: 3.8
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
?Mitochondrial complex I deficiency, nuclear type 30, OMIM:301021; Linear skin defects with multiple congenital anomalies 3, OMIM:300952
Publications
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.
Panel Version: 2.10
Comment on list classification: Following clinical review, it was agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update.Created: 9 Aug 2022, 1:13 p.m. | Last Modified: 9 Aug 2022, 1:13 p.m.
Panel Version: 1.886
This gene and phenotype were reviewed during a meeting on 21st July 2022 between representatives of the North Thames and Central & South R21 testing GLHs.
Clinical review and curation was performed by Lyn Chitty, Alison Male, Rhiannon Mellis (North Thames GLH), and Stephanie Allen, Denise Williams, Esther Kinning and Anna de Burca (Central & South GLH).
Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Currently rated Green on the following other PanelApp panel(s): mitochondrial and childhood cardiomyopathy panels.
Details of review:
Van Rahden et al. (2015) (PMID: 25772934) reported 2 unrelated girls with linear skin defects of the face and neck at birth, cardiomyopathy, and various other congenital anomalies. One of them had ACC and dilated lateral ventricles on prenatal ultrasound. There was a second affected female pregnancy in the same family with thickened myocardium and pericardial effusion, corpus-callosum dysgenesis, a small cerebellum, and a connection between a lateral ventricle and the cavum septum pellucidum, as well as intrauterine growth retardation (confirmed to have the same variant). The mother was also heterozygous for the variant but unaffacted, with skewed X-inactivation.
Also identified on gene agnostic re-analysis of a fetal case tested in the GMS: heterozygous de novo pathogenic variant in a female with ACC, VSD, ventricular hypertrophy, polyhydramnios.Created: 1 Aug 2022, 6:02 p.m. | Last Modified: 1 Aug 2022, 6:02 p.m.
Panel Version: 1.880
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
Linear skin defects; cardiomyopathy; ACC
Publications
DDG2P rating in original PAGE list: Probable for MICROPHTHALMIA WITH LINEAR SKIN DEFECTS SYNDROMECreated: 11 Dec 2018, 9:05 a.m.
Phenotypes for gene: NDUFB11 were changed from Linear skin defects with multiple congenital anomalies 3, OMIM:300952; Cardiomyopathy; Agenesis of corpus callosum (ACC) to ?Mitochondrial complex I deficiency, nuclear type 30, OMIM:301021; Linear skin defects with multiple congenital anomalies 3, OMIM:300952; Cardiomyopathy; Agenesis of corpus callosum (ACC)
Tag Q3_22_rating was removed from gene: NDUFB11. Tag Q3_22_NHS_review was removed from gene: NDUFB11.
Source Expert Review Green was added to NDUFB11. Source NHS GMS was added to NDUFB11. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: ndufb11 has been classified as Amber List (Moderate Evidence).
Publications for gene: NDUFB11 were set to
Phenotypes for gene: NDUFB11 were changed from MICROPHTHALMIA WITH LINEAR SKIN DEFECTS SYNDROME to Linear skin defects with multiple congenital anomalies 3, OMIM:300952; Cardiomyopathy; Agenesis of corpus callosum (ACC)
Tag Q3_22_rating tag was added to gene: NDUFB11. Tag Q3_22_NHS_review tag was added to gene: NDUFB11.
gene: NDUFB11 was added gene: NDUFB11 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: NDUFB11 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: NDUFB11 were set to MICROPHTHALMIA WITH LINEAR SKIN DEFECTS SYNDROME