Carriers of pathogenic variants in both BRCA1 and BRCA2 genes as a double mutation (BRCA1/2 DM) have been rarely reported in women with epithelial ovarian cancer (EOC).
We reviewed the English literature and interrogated three repositories reporting EOC patients carrying BRCA1/2 DM. The clinicopathological parameters of 36 EOC patients carrying germline BRCA1/2 DM were compared to high-grade serous EOC women of the COEUR cohort with known germline BRCA1/BRCA2 mutation carrier status (n = 376 non-carriers, n = 65 BRCA1 and n = 38 BRCA2). Clinicopathological parameters evaluated were age at diagnosis, stage of disease, loss of heterozygosity, type of mutation, immunohistochemistry profile, progression occurrence and survival.
Median age at diagnosis of BRCA1/2 DM patients was 51.9 years, similar to BRCA1 mutation carriers (49.7 years, p = .58) and younger than BRCA2 mutation carriers (58.1 years, p = .02). Most patients were diagnosed at advanced stage (III-IV; 82%) and were carriers of founder/frequent mutations (69%). Tissue immunostainings revealed no progesterone receptor expression and low intraepithelial inflammation. The 5-year survival rate (60%) was significantly lower than that of BRCA2 mutation carriers (76%, p = .03) but not of BRCA1 mutation carriers (51%, p = .37).
Our data suggests some co-dominant effect of both mutations but the outcome of these patients more closely resembled that of BRCA1 mutation carriers with poor prognosis factors.

METHODS: Monogenic diseases are important models for the study of neurodegenerative diseases, such as Parkinson\'s disease (PD) and dementia. Notably, for some disorders, homozygosity is associated with a complex metabolic disease, while heterozygosity predisposes to late-onset neurodegeneration. For instance, biallelic glucocerebrosidase gene mutations cause Gaucher\'s disease, while heterozygous mutations are a common genetic risk factor for late-onset PD. Little is known about similar risks of related diseases, such as Niemann-Pick type C (NPC). Given that both conditions map into related, i.e., lysosomal, pathways, we hypothesize a similar risk of single-NPC gene mutations. Indeed, there is increasing evidence based on clinical observations in humans and animal studies. Here we review the current knowledge of NPC heterozygosity.
RESULTS: Family history studies suggest a high proportion of late-onset neurodegenerative diseases in NPC families. We identified 19 cases with heterozygous NPC mutations in the literature who presented with a neurodegenerative disease, including levodopa-responsive PD, atypical parkinsonism (PSP, CBD), dystonia or dementia with a mean age at onset of about 57 years (range 8-87). Consistent splenomegaly and mildly abnormal filipin staining results have also been reported in heterozygous gene mutation carriers. Imaging and pathological data support this notion.
CONCLUSIONS: This finding has wider implications in so far as NPC-related forms of Parkinsonian syndromes, dementia, motor neuron disease and other neurodegenerative disorders may benefit from NPC-mechanistic therapies, in particular related to lysosomal dysfunction. Further research is warranted to generate systematic data of heterozygous mutation carriers, including longitudinal data.

During microsatellite marker development, researchers must choose from a pool of possible primer pairs to further test in their species of interest. In many cases, the goal is maximizing detectable levels of genetic variation. To guide researchers and determine which markers are associated with higher levels of genetic variation, we conducted a literature review based on 6782 genomic microsatellite markers published from 1997-2012. We examined relationships between heterozygosity (H e or H o) or allele number (A) with the following marker characteristics: repeat type, motif length, motif region, repeat frequency, and microsatellite size. Variation across taxonomic groups was also analyzed. There were significant differences between imperfect and perfect repeat types in A and H e. Dinucleotide motifs exhibited significantly higher A, H e, and H o than most other motifs. Repeat frequency and motif region were positively correlated with A, H e, and H o, but correlations with microsatellite size were minimal. Higher taxonomic groups were disproportionately represented in the literature and showed little consistency. In conclusion, researchers should carefully consider marker characteristics so they can be tailored to the desired application. If researchers aim to target high genetic variation, dinucleotide motif lengths with large repeat frequencies may be best.