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Hearing loss

Gene: SERAC1

Green List (high evidence)

SERAC1 (serine active site containing 1)
EnsemblGeneIds (GRCh38): ENSG00000122335
EnsemblGeneIds (GRCh37): ENSG00000122335
OMIM: 614725, Gene2Phenotype
SERAC1 is in 16 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on publications: added publications form expert review to support phenotype
Created: 19 Dec 2017, 11:20 a.m.
Comment on list classification: changed Red to Green from expert review and new evidence in the literature
Created: 19 Dec 2017, 11:19 a.m.
Wortmann et al (2017) PMID: 29205472 reclassified MEGDEL syndrome to MEGDHEL syndrome, 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome (MEGDHEL) as they found that liver involvement was an additional clinical feature, so Hepatopathy was incorporated into the acronym. From a study of 67 individuals (39 previously unreported) from 59 families were included (age range 5 days - 33.4 years, median age 9 years) Wortmann et al idenitified 41 different SERAC1 biallelic variants, including 20 that have not been reported before. With exception of two families with a milder phenotype, all affected individuals show a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia was seen in more than 40% of all cases. Starting at a median age of six months muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learnt to walk (68%). 79% suffered hearing loss, 58% never learnt to speak, nearly all had significant intellectual disability (88%).
Created: 19 Dec 2017, 11:18 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; MEGDEL syndrome; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; MEGDHEL syndrome

Publications

Jun Shen (Harvard Medical School)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#614739:3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome[Failure to thrive; Hearing loss, sensorineural; Feeding problems; HypotoniaDegrading mitochondria; Psychomotor retardationPsychomotor regressionMental retardationSpasticityDystoniaExtrapyramidal symptomsSeizures (less common)Leigh syndromeLesions in the basal gangliaBrain atrophyCerebellar atrophy; Lactic acidosisHypoglycemia; Recurrent infectionsNeonatal sepsis; Increased serum lactateDefects in mitochondrial oxidative phosphorylation3-methylglutaconic aciduriaAbnormal phospholipid profileAbnormal phosphatidylglycerol profile (increased 34-to-1 and decreased 36-to-1 ratio)Abnormal cardiolipin subspecies compositionIntracellular accumulation of unesterified cholesterolDecreased serum cholesterol (in some)Elevated serum transaminase levelsHyperammonemiaElevated serum alpha-fetoproteinCoagulopathy (INR = 2.2 - 3.5)]

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739
  • MEGDEL syndrome
  • 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome
  • MEGDHEL syndrome
OMIM
614725
Clinvar variants
Variants in SERAC1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

19 Dec 2017, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for SERAC1 were set to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; MEGDEL syndrome; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; MEGDHEL syndrome

19 Dec 2017, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for SERAC1 were set to 29205472; 22683713; 16527507; 28482397; 28778788; 27186703; 27604308; 23707711; 16527507

19 Dec 2017, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for SERAC1 was changed from to BIALLELIC, autosomal or pseudoautosomal

19 Dec 2017, Gel status: 3

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SERAC1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen