Fetal anomalies
Gene: TMEM70
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, 2:08 p.m. | Last Modified: 9 Aug 2022, 2:08 p.m.
Panel Version: 1.898
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.
Details of review:
PMID: 21147908
The previously described clinical spectrum was expanded to include infantile onset cataract, early onset gastrointestinal dysfunction and congenital hypertonia with multiple contractures resembling arthrogryposis. The first characterisation of fetal presentation of the syndrome is also provided, featuring significant intrauterine growth retardation, severe oligohydramnios, fetal hypotonia, and myocardial wall thickening.
PMID: 24740313 - 'All showed intrauterine growth restriction (IUGR) and most of them had an emergency delivery because of oligohydramnios, indicating antenatal disease onset.'
PMID: 26550569 - Pregnancies with affected children - all had anhydramnion, 2 had reduced movements.
PMID: 20335238 - Paper on course of disease in 25 reported patients. ‘68% of patients were delivered prematurely and intrauter-ine growth retardation (IUGR) was present in 58%.’
PMID: 25326274 Magner 2015 - Long term outcome of 48 patients
'Oligohydramnios or anhydramnios were present in 14 of 35 mothers (40 %) for whom data were available. Fetal sonography revealed HCM in five of 24 analysed cases (21 %). Median gestational age at birth was 36 weeks (range 28–41) and median birth weight was 2060 g (range 690-3080 g). Intrauterine growth retardation (IUGR) was present in 47 % of children'
Gene agnostic reanalysis of a fetal case tested in the GMS found biallelic TMEM70 variants in a baby that had Antenatal diagnosis of increased nuchal translucency (6.3mm) , Left congenital diaphragmatic hernia, right ventricle hypertrophy, tricuspid regurgitation, and IUGR.
Delivered by elective section at 34 weeks for IUGR/CDH concerns. Birthweight at 20th percentile. No reported dysmorphic features.Created: 1 Aug 2022, 5:51 p.m. | Last Modified: 1 Aug 2022, 5:51 p.m.
Panel Version: 1.880
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
IUGR; Oligohydramnios; Anhydramnios; Cardiomyopathy
Publications
This gene was reviewed by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Presentation of mitochondrial disorders can be variable, and most aren't obvious at birth. Therefore exclude unless the gene has been directly associated with a fetal presentation.Created: 25 Jul 2019, 8:04 a.m. | Last Modified: 25 Jul 2019, 8:04 a.m.
Panel Version: 0.311
DDG2P rating in original PAGE list: Confirmed for MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2Created: 11 Dec 2018, 9:05 a.m.
Publications
Tag Q3_22_rating was removed from gene: TMEM70. Tag Q3_22_NHS_review was removed from gene: TMEM70.
Source Expert Review Green was added to TMEM70. Source NHS GMS was added to TMEM70. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: TMEM70 were set to
Phenotypes for gene: TMEM70 were changed from MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2 to IUGR; Oligohydramnios; Anhydramnios; Cardiomyopathy
Gene: tmem70 has been classified as Amber List (Moderate Evidence).
Tag Q3_22_rating tag was added to gene: TMEM70. Tag Q3_22_NHS_review tag was added to gene: TMEM70.
Source Expert Review Red was added to TMEM70. Rating Changed from Green List (high evidence) to Red List (low evidence)
gene: TMEM70 was added gene: TMEM70 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: TMEM70 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TMEM70 were set to MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2