Evidence of mild founder LMOD3 mutations causing nemaline myopathy 10 in Germany and Austria.

OBJECTIVE: To expand the clinical and genetic spectrum of nemaline myopathy 10 by a series of Austrian and German patients with a milder disease course and missense mutations in LMOD3. METHODS: We characterized the clinical features and the genetic status of 4 unrelated adolescent or adult patients with nemaline myopathy. RESULTS: The 4 patients showed a relatively mild disease course. They all have survived into adulthood, 3 of 4 have remained ambulatory, and all showed marked facial weakness. Muscle biopsy specimens gave evidence of nemaline bodies. All patients were unrelated but originated from Austria (Tyrol and Upper Austria) and Southern Germany (Bavaria). All patients carried the missense variant c.1648C>T, p.(Leu550Phe) in the LMOD3 gene, either on both alleles or in trans with another missense variant (c.1004A>G, p.Gln335Arg). Both variants were not reported previously. CONCLUSIONS: In 2014, a severe form of congenital nemaline myopathy caused by disrupting mutations in LMOD3 was identified and denoted as NEM10. Unlike the previously reported patients, who had a severe clinical picture with a substantial risk of early death, our patients showed a relatively mild disease course. As the missense variant c.1648C>T is located further downstream compared to all previously published LMOD3 mutations, it might be associated with higher protein expression compared to the reported loss-of-function mutations. The apparent clusters of 2 mild mutations in Germany and Austria in 4 unrelated families may be explained by a founder effect.

Histopathology of human corneas after amniotic membrane and limbal stem cell transplantation for severe chemical burn.

PURPOSE: To describe the histopathologic changes in the cornea following amniotic membrane transplantation (AMT) combined with limbal transplantation. METHODS: Four eyes with complete limbal stem cell deficiency after severe chemical burn underwent AMT with either a living-related conjunctival limbal allograft (lr-CLAL) (three eyes) or a conjunctival limbal autograft (CLAU) (one eye) for ocular surface reconstruction. Penetrating keratoplasty was performed several months after the initial procedure for further visual rehabilitation. Mean follow up time was 20 months. Light and transmission electron microscopy (TEM) and indirect immunofluorescence microscopy of the excised corneal buttons were performed. RESULTS: All specimens displayed a multilayered epithelium without conjunctival goblet cells over the entire corneal surface. Basal epithelial cells demonstrated a firm connection to the remnants of the transplanted amniotic membrane (AM), which at some places appeared to be in a state of "modification" or "remodeling" in the collagen layers. The basement membrane zone displayed a positive staining when using antibodies against collagen IV and VII, integrin alpha6 and beta4, laminin 5, and bullous pemphigoid antigen 2. Remnants of the AM in the specimen showed staining of collagen IV, which was found also in cross-sections of cryopreserved AM. The recipients Bowman's membranes that were only partially present after the initial trauma were significantly disturbed. CONCLUSION: Within the time frame studied, the transplanted AM apparently survives and integrates into the host tissue being modified or remodeled by recipient cells. AMT in combination with a CLAU or lr-CLAL is a useful technique in promoting a rapid and stable reepithelialization of a corneal surface following severe chemical or thermal damage.

Feline orthopoxvirus infection transmitted from cat to human.

We report the case of a 56-year-old female patient who presented with an inflamed, ulcerated lesion on the left side of her neck after contact (scratch) with a cat living in the patient's house. Satellite lesions developed despite local treatment and parenteral clindamycin. Histopatholgic examination and the Tzanck test showed evidence of a viral infection. Subsequent transmission electron microscopy of scrap tissue and material from a fresh pustule exhibited multiple typical poxvirus particles, predominantly in remnants of scaled-off layers of degenerated keratinocytes, and virus particles in intermingled phagocytes, leading to the diagnosis of feline Orthopoxvirus (cowpox virus) infection. These results were verified by polymerase chain reaction and sequencing. Concern has been raised as to whether discontinuation of smallpox vaccine would cause an increase in Orthopoxvirus infection, but this has not yet shown to be the case.