Alternative titles; symbols
HGNC Approved Gene Symbol: LRMDA
SNOMEDCT: 722059002;
Cytogenetic location: 10q22.2-q22.3 Genomic coordinates (GRCh38) : 10:75,431,624-76,560,168 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 10q22.2-q22.3 | Albinism, oculocutaneous, type VII | 615179 | Autosomal recessive | 3 |
Tzschach et al. (2010) determined that the C10ORF11 gene contains 6 exons.
By genomic sequence analysis, Tzschach et al. (2010) mapped the C10ORF11 gene to chromosome 10q22.3.
Using immunohistochemistry, Gronskov et al. (2013) demonstrated localization of C10ORF11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. The authors stated that the localization pattern was consistent with a gene that is important for, and acts cell-autonomously in, melanocyte differentiation and function. Morpholino knockdown of the zebrafish homolog resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wildtype C10ORF11, but not by mutant C10ORF11.
Tzschach et al. (2010) reported 3 unrelated children with mental retardation and variable dysmorphic features who had a heterozygous interstitial deletion of chromosome 10q22.3 including the C10ORF11 gene. The deletions ranged from 3.2 to 7.9 Mb. The patient with the largest deletion had more complex clinical features, including feeding problems, sensorineural hearing loss, and dysmorphic features such as hypertelorism, low-set ears, retrognathia, small nose, and elongated thumbs. Brain MRI showed delayed myelination, and she had severely retarded psychomotor development without speech at age 3 years, 9 months. A fourth child with delayed psychomotor development, ataxic gait, myopia, and strabismus had a translocation t(10;13)(q22.3;p13) that interrupted the C10ORF11 gene. Tzschach et al. (2010) concluded that haploinsufficiency of C10ORF11 contributed to the cognitive defects in these patients.
In 6 probands from the Faroe Islands with oculocutaneous albinism (OCA7; 615179), Gronskov et al. (2013) identified homozygosity for a nonsense mutation (R194X; 614537.0001) in the C10ORF11 gene. Analysis of 92 Faroese controls detected 3 heterozygous carriers of R194X, corresponding to a carrier frequency of 3.3%. In addition, a patient of Lithuanian origin was apparently homozygous for a 1-bp duplication in C10ORF11 (614537.0002).
In 6 probands from the Faroe Islands with oculocutaneous albinism (OCA7; 615179), Gronskov et al. (2013) identified homozygosity for a 580C-T transition in exon 6 of the C10ORF11 gene, resulting in an arg194-to-ter (R194X) substitution. Cosegregation of the mutation and disease was confirmed in 5 of the 6 families. Analysis of 92 Faroese controls detected 3 heterozygous carriers of R194X, corresponding to a carrier frequency of 3.3%.
In a patient of Lithuanian origin with oculocutaneous albinism (OCA7; 615179), Gronskov et al. (2013) identified apparent homozygosity for a 1-bp duplication (66dupC) in exon 2 of the C10ORF11 gene, causing a frameshift predicted to result in premature termination (A23Rfs*39). The authors noted that a deletion on 1 allele could not be ruled out, nor could preferential amplification of 1 allele because of sequence variation on the second allele.
Gronskov, K., Dooley, C. M., Ostergaard, E., Kelsh, R. N., Hansen, L., Levesque, M. P., Vilhelmsen, K., Mollgard, K., Stemple, D. L., Rosenberg, T. Mutations in C10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism. Am. J. Hum. Genet. 92: 415-421, 2013. [PubMed: 23395477] [Full Text: https://doi.org/10.1016/j.ajhg.2013.01.006]
Tzschach, A., Bisgaard, A.-M., Kirchhoff, M., Graul-Neumann, L. M., Neitzel, H., Page, S., Ahmed, A., Muller, I., Erdogan, F., Ropers, H.-H., Kalscheuer, V. M., Ullmann, R. Chromosome aberrations involving 10q22: report of three overlapping interstitial deletions and a balanced translocation disrupting C10orf11. Europ. J. Hum. Genet. 18: 291-295, 2010. [PubMed: 19844253] [Full Text: https://doi.org/10.1038/ejhg.2009.163]