Phenylalanine hydroxylase deficiency exhibits mutation heterogeneity in two large old order Amish settlements

Das Deutsch Center (DDC) Clinic for Special Needs Children, Middlefield, Ohio 44062, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.05). 08/2007; 143A(16):1938-40. DOI: 10.1002/ajmg.a.31852
Source: PubMed
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    ABSTRACT: Hypertrophic cardiomyopathy is one of the most common inherited cardiac disorders, with a prevalence of 1:500 in the general population. We have recently reported a severe neonatal hypertrophic cardiomyopathy caused by a novel homozygous splice site c.3330 + 2 T > G mutation in the MYBPC3 gene in an Amish community. The affected children typically presented with signs and symptoms of congestive heart failure during the first three weeks of life, and most of them died before one year of age unless they received a heart transplant. Since the condition is inherited in an autosomal dominant pattern with incomplete penetrance, further studies to understand the clinical course in the heterozygous carrier of c.3330 + 2 T > G mutation were performed when we provided the service of carrier testing in the community. The preliminary results indicated a relatively low incidence of the phenotypic expression of hypertrophic cardiomyopathy, although the disease was identified in a few heterozygous carriers before they reached to their adolescence. Significant variation of the phenotypic expression suggests the complexity of the disease development. The Amish community is often composed of genetically and geographically isolated, large, multigenerational families with similar environmental influences, and potentially harbors a reduced number of risk factors compared to a more heterogeneous population. Therefore, our further study will not only benefit the Amish population but also will help us to understand the hypertrophic cardiomyopathy as a whole, for the disease development, diagnosis, treatment, and prognosis. Partnering with the community to establish solid, trustful relationships with the affected families and to provide much needed services to them has been the key to success in the past and will remain essential for our future study.
    Progress in Pediatric Cardiology 05/2011; 31(2):129-134. DOI:10.1016/j.ppedcard.2011.02.011


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