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Infantile nystagmus syndrome (INS) denominates early-onset, involuntary oscillatory eye movements with different etiologies. Nystagmus is also one of the symptoms in oculocutaneus albinism (OCA), a heterogeneous disease mainly caused by defects in melanin synthesis or melanosome biogenesis. Dopachrome tautomerase (DCT, also called TYRP2) together with tyrosinase (TYR) and tyrosin-related protein 1 (TYRP1) is one of the key enzymes in melanin synthesis. Although DCT´s role in pigmentation has been proven in different species, until now only mutations in TYR and TYRP1 have been found in patients with OCA. Detailed ophthalmological and orthoptic investigations identified a consanguineous family with two individuals with isolated infantile nystagmus and one family member with subtle signs of albinism. By whole-exome sequencing and segregation analysis, we identified the missense mutation c.176G > T (p.Gly59Val) in DCT in a homozygous state in all three affected family members. We show that this mutation results in incomplete protein maturation and targeting in vitro compatible with a partial or total loss of function. Subsequent screening of a cohort of patients with OCA (n = 85) and INS (n = 25) revealed two heterozygous truncating mutations, namely c.876C > A (p.Tyr292*) and c.1407G > A (p.Trp469*), in an independent patient with OCA. Taken together, our data suggest that mutations in DCT can cause a phenotypic spectrum ranging from isolated infantile nystagmus to oculocutaneous albinism.

Introduction: Failure of acetabular components often leads to bone loss with extensive elongated defects in the surrounding bone. In these cases, reconstruction is challenging and stable fixation of the revision implant difficult. The use of an oblong cup has been described as an option for acetabular reconstruction in such revisions. We report the first long-term results obtained with this implant to date., Materials and Methods: Fifty-six longitudinal oblong revision cups (LOR) were evaluated clinically and radiologically after a follow-up of 8-12 years (average 9 years). The defects treated with the LOR cup ranged from Paprosky type 1-3. Allogenic cancellous bone chips were additionally used in 31 reconstructions to fill cavitary defects., Results: Based on radiological criteria, 50 acetabular implants underwent osseointegration without any definitive signs of loosening; 2 consistently exhibited zonal radiolucent lines that were always smaller than 2 mm, 1 migrated by around 3 mm. None of these cases exhibited any clinical symptoms. In 11 cases where acetabular defects manifested postoperatively, 8 were remodeled completely and 3 partially at final follow-up. Three revision implants migrated farther than 5 mm and had to be revised before 32-month follow-up. In addition, 1 septic implant failure occurred. After an average follow-up of 9 years, 93% of the investigated implants remained in situ without further revision and 95% without aseptic implant failure., Conclusion: This 12-year clinical study demonstrates that the LOR cup offers a successful concept for the revision of failed acetabular components that also promotes the biological reconstruction of bony defects. Compared with other methods with similarly long follow-ups, our long-term results prove this procedure has a very low rate of revision and aseptic implant failure.