Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy Provides Insights into Duplication Mechanisms and Allele‐Specific Expression

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication‐based mechanisms such fork stalling and template switching or microhomology‐mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients’ fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele‐specific LMNB1 expression levels.     

Intrapericardial Immature Teratoma with Successful Treatment in a Neonate

Intra-pericardial teratoma, most often a benign tumor, is an extremely rare condition in a newborn. It can be a diagnostic and therapeutic challenge if it presents with massive pericardial effusion. Complete surgical excision of the tumor is necessary because of its association with tissues of malignant potential. A 16-d-old newborn was diagnosed with intra pericardial immature teratoma (IT) and managed successfully with multidisciplinary team approach by prompt referral for complete surgical resection followed by adjuvant chemotherapy with carboplatin, etoposide and bleomycin (JEB) to prevent recurrence. The infant is now on close follow up with monitoring of serum alpha fetoprotein (AFP) levels and imaging studies for early diagnosis of recurrence of tumor and chemotherapy related complications.