Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratoire de Génétique Moléculaire, |
RCV001270366 | SCV001337677 | likely pathogenic | Albinism | 2020-06-15 | no assertion criteria provided | clinical testing | We sequenced a panel of genes with known or predicted involvement in melanogenesis in 230 unsolved albinism patients in order to search for new mutations. In two unrelated patients we identified variants in the Dopachrome tautomerase (DCT) (also called Tyrosinase-related protein 2, TYRP2) gene. One patient was compound heterozygous for a 14 bp deletion in exon 9 and a c.118T>A p.(Cys40Ser) variant. The second patient was homozygous for a c.183C>G p.(Cys61Trp) variant. Both patients had mild hair and skin hypopigmentation, and classical ocular features including nystagmus, iris and retinal hypopigmentation. We have used CRISPR/Cas9 in C57BL/6J mice to create mutations identical to the missense mutations carried by these two patients, along with one loss-of-function indel mutation. When bred to homozygosity these novel mouse mutations revealed different degrees of hypopigmentation of the coat, milder for Cys40Ser compared to Cys61Trp or the frameshift mutation. Histological analysis of the retina identified significant hypopigmentation of the retinal pigmented epithelium (RPE) indicating that a defect in RPE melanogenesis could be associated with eye and vision defects in DCT patients. |
| OMIM | RCV001290119 | SCV001478267 | pathogenic | Oculocutaneous albinism type 8 | 2021-04-20 | no assertion criteria provided | literature only |