PMID- 38137040
OWN - NLM
STAT- MEDLINE
DCOM- 20231225
LR  - 20231225
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 14
IP  - 12
DP  - 2023 Dec 14
TI  - Compilation of Genotype and Phenotype Data in GCDH-LOVD for Variant 
      Classification and Further Application.
LID - 10.3390/genes14122218 [doi]
LID - 2218
AB  - Glutaric aciduria type 1 (GA-1) is a rare but treatable autosomal-recessive 
      neurometabolic disorder of lysin metabolism caused by biallelic pathogenic 
      variants in glutaryl-CoA dehydrogenase gene (GCDH) that lead to deficiency of 
      GCDH protein. Without treatment, this enzyme defect causes a neurological 
      phenotype characterized by movement disorder and cognitive impairment. Based on a 
      comprehensive literature search, we established a large dataset of GCDH variants 
      using the Leiden Open Variation Database (LOVD) to summarize the known genotypes 
      and the clinical and biochemical phenotypes associated with GA-1. With these 
      data, we developed a GCDH-specific variation classification framework based on 
      American College of Medical Genetics and Genomics and the Association for 
      Molecular Pathology guidelines. We used this framework to reclassify published 
      variants and to describe their geographic distribution, both of which have 
      practical implications for the molecular genetic diagnosis of GA-1. The freely 
      available GCDH-specific LOVD dataset provides a basis for diagnostic laboratories 
      and researchers to further optimize their knowledge and molecular diagnosis of 
      this rare disease.
FAU - Tibelius, Alexandra
AU  - Tibelius A
AD  - Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, Germany.
FAU - Evers, Christina
AU  - Evers C
AD  - Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, Germany.
FAU - Oeser, Sabrina
AU  - Oeser S
AUID- ORCID: 0009-0007-1915-5415
AD  - Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, Germany.
FAU - Rinke, Isabelle
AU  - Rinke I
AD  - Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, Germany.
FAU - Jauch, Anna
AU  - Jauch A
AD  - Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, Germany.
FAU - Hinderhofer, Katrin
AU  - Hinderhofer K
AD  - Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20231214
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - EC 1.3.8.6 (Glutaryl-CoA Dehydrogenase)
RN  - Glutaric Acidemia I
SB  - IM
MH  - Humans
MH  - *Brain Diseases, Metabolic/diagnosis
MH  - Glutaryl-CoA Dehydrogenase
MH  - Phenotype
MH  - Genotype
PMC - PMC10742628
OTO - NOTNLM
OT  - GCDH
OT  - LOVD
OT  - geographic distribution
OT  - glutaric acidemia
OT  - glutaric aciduria
OT  - glutaryl-CoA dehydrogenase
OT  - inborn errors of metabolism
OT  - variant classification
OT  - variant interpretation
OT  - variation database
COIS- The authors declare no conflict of interest.
EDAT- 2023/12/23 12:43
MHDA- 2023/12/25 06:41
PMCR- 2023/12/14
CRDT- 2023/12/23 01:07
PHST- 2023/11/19 00:00 [received]
PHST- 2023/12/06 00:00 [revised]
PHST- 2023/12/12 00:00 [accepted]
PHST- 2023/12/25 06:41 [medline]
PHST- 2023/12/23 12:43 [pubmed]
PHST- 2023/12/23 01:07 [entrez]
PHST- 2023/12/14 00:00 [pmc-release]
AID - genes14122218 [pii]
AID - genes-14-02218 [pii]
AID - 10.3390/genes14122218 [doi]
PST - epublish
SO  - Genes (Basel). 2023 Dec 14;14(12):2218. doi: 10.3390/genes14122218.