Likely inborn error of metabolism

Gene: SLC31A1

I don't know

Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.

Created: 2 Mar 2023, 9:59 p.m. | Last Modified: 2 Mar 2023, 9:59 p.m.

Panel Version: 3.13

Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.

Created: 2 Mar 2023, 9:58 p.m. | Last Modified: 2 Mar 2023, 9:58 p.m.

Panel Version: 3.13

Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.

Created: 2 Mar 2023, 9:58 p.m. | Last Modified: 2 Mar 2023, 9:58 p.m.

Panel Version: 3.13

Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.

Created: 2 Mar 2023, 9:57 p.m. | Last Modified: 2 Mar 2023, 9:57 p.m.

Panel Version: 3.12

Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.

Created: 2 Mar 2023, 9:57 p.m. | Last Modified: 2 Mar 2023, 9:57 p.m.

Panel Version: 3.12

Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.

Created: 2 Mar 2023, 9:56 p.m. | Last Modified: 2 Mar 2023, 9:56 p.m.

Panel Version: 3.12

PMID:35913762 reported an identical twin male infants identified with homozygous novel missense variant p.Arg95His in CTR1. The twins had hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency. In addition, the CSF copper levels were lower and functional studies including structural modelling of the variant showed impaired copper transport. Treatment with copper Histidinate in the patients' cultured cells and in the patients normalized CCO activity and enhanced mitochondrial respiration in vitro, and was associated with modest clinical improvements.

PMID:36562171 reported a newborn infant of consanguineous parents with a homozygous pathogenic variant p.Leu79Pro in CTR1. This infant was born with pulmonary hypoplasia. At two weeks of age, multifocal brain hemorrhages were diagnosed and the infant developed seizures. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. The infant died at one month of age.
Sources: Literature

Created: 2 Mar 2023, 9:54 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder, MONDO:0700092

Publications

• 35913762
• 36562171