Alternative titles; symbols
SNOMEDCT: 1003387003; ORPHA: 308400, 833, 99732; DO: 0111166;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 14q23.3-q24.1 | Molybdenum cofactor deficiency C | 615501 | Autosomal recessive | 3 | GPHN | 603930 |
A number sign (#) is used with this entry because of evidence that molybdenum cofactor deficiency type C (MOCODC) is caused by homozygous mutation in the GEPH gene (GPHN; 603930) on chromosome 14q23.
For a general phenotypic description and a discussion of genetic heterogeneity of molybdenum cofactor deficiency, see MOCODA (252150).
Reiss et al. (2001) studied the last of 3 affected infants born to a Danish mother and father who were cousins. All 3 died in the neonatal period (at day 12, 29, and 3) with symptoms identical to those of molybdenum cofactor (MoCo) deficiency. Three other pregnancies of the mother resulted in 2 healthy sibs and 1 spontaneous abortion. The first affected infant was a boy; the other 2 were girls. All showed hypotonia combined with hyperreflexia, as well as tonic-clonic convulsions. Fibroblasts of the third infant were used to verify molybdenum cofactor deficiency by biochemical and in vitro complementation assays.
Reiss et al. (2011) reported a female infant, born of consanguineous Algerian parents, with MOCODC. She presented in the neonatal period with global hypotonia, feeding difficulties, and generalized seizures. Brain MRI showed cortical and subcortical lesions, abnormalities in the basal ganglia, and hypoplastic pons and cerebellum. The cerebellum showed polymicrogyria. Laboratory studies showed a positive sulfite test and were consistent with MOCODC. The seizures remained intractable. At age 2 years, she had severe axial hypotonia and peripheral hypertonia, with no head control or visual contact.
The transmission pattern of molybdenum cofactor deficiency type C in the family reported by Reiss et al. (2001) was consistent with autosomal recessive inheritance.
In a Dutch patient, born of consanguineous parents, with molybdenum cofactor deficiency type C, Reiss et al. (2001) identified a homozygous deletion in the GEPH gene (603930.0001).
Reiss and Johnson (2003) collected a total of 32 different disease-causing mutations in the MOCS1, MOCS2, or GPHN genes, including several common to more than 1 family, that had been identified in molybdenum cofactor-deficient patients and their relatives.
In an Algerian girl with MOCODC, Reiss et al. (2011) identified a homozygous mutation in the GPHN gene (D580A; 603930.0003).
Reiss, J., Gross-Hardt, S., Christensen, E., Schmidt, P., Mendel, R. R., Schwarz, G. A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency. Am. J. Hum. Genet. 68: 208-213, 2001. [PubMed: 11095995] [Full Text: https://doi.org/10.1086/316941]
Reiss, J., Johnson, J. L. Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH. Hum. Mutat. 21: 569-576, 2003. [PubMed: 12754701] [Full Text: https://doi.org/10.1002/humu.10223]
Reiss, J., Lenz, U., Aquaviva-Bourdain, C., Joriot-Chekaf, S., Mention-Mulliez, K., Holder-Espinasse, M. A GPHN point mutation leading to molybdenum cofactor deficiency. (Letter) Clin. Genet. 80: 598-599, 2011. [PubMed: 22040219] [Full Text: https://doi.org/10.1111/j.1399-0004.2011.01709.x]