Bahig M. Shehata, MD
Genetic Analysis to Identify Inheritance Patterns in Histiocytoid Cardiomyopathy
Emory University School of Medicine, Atlanta, GA
2016 Amount Awarded – $49,552
Histiocytoid cardiomyopathy (HC) is a rare form of cardiomyopathy, observed predominantly in newborn females, which is fatal unless treated early in life. Over 100 HC cases have been reported in the literature, but the prevalence is likely to be higher since many cases may have been misdiagnosed as Sudden Infant Death Syndrome (SIDS). The molecular genetic basis of HC was unknown despite several hypotheses in medical literature. After observing familial tendency, a HC registry was started in order to collect clinical data and perform analyses with the objective of identifying the causative gene(s). The registry currently houses over 150 cases and further registry details can be found at spponline.org. A casual gene was recently identified in the form of a premature stop codon in multiple cases of HC involving the NDUFB11 gene, which was published in American Journal of Medical Genetics in April 2015. This discovery was the first breakthrough in the molecular genetic basis of HC. Data from the registry indicates a 5% familial tendency; however, the true percentage is likely much higher, as several families have reported several unexplained miscarriages. The proposed study will analyze families with multiple HC cases and families with a single affected child in order to further explore the molecular and genetic basis of HC including, the familial tendency. DNA will be extracted, and targeted exome sequencing of both whole blood samples of family members and the living affected children, as well as samples from paraffin embedded tissue from the deceased affected patients will be completed. Understanding the effect of mutations in HC patients on mitochondrial function will allow for new therapeutic interventions to be developed for affected children, as well as offer opportunities to improve prevention, monitoring, and early treatment of identified carriers.