Mendelian disease research in the Plain populations of Lancaster County, Pennsylvania

Abstract

Founder populations have long contributed to our knowledge of rare disease genes and phenotypes. From the pioneering work of Dr. Victor McKusick to today, research in these groups has shed light on rare recessive phenotypes, expanded the clinical spectrum of disease, and facilitated disease gene identification. Current clinical and research studies in these special groups augment the wealth of knowledge already gained, provide new insights into emerging problems such as variant interpretation and reduced penetrance, and contribute to the development of novel therapies for rare genetic diseases. Clinical developments over the past 30 years have altered the fundamental relationship with the Lancaster Plain communities: research has become more collaborative, and the knowledge imparted by these studies is now being harnessed to provide cutting‐edge translational medicine to the very community of vulnerable individuals who need it most.

Festschrift for Victor A. McKusick on the Centenary of his Birth: Introduction

“…The next several papers provide a view to the future of medical genetics including options for treatment of Mendelian disorders and how this future was informed by McKusick's groundbreaking work. The first paper in this section is a paper by Puffenberger (2021) titled “Mendelian Disease Research in the Plain Populations of Lancaster County, Pennsylvania.” This article begins with a discussion of McKusick's initial work with the Amish population, first focusing on a cluster of cases of what was thought to be achondroplasia, but was later recognized to be two autosomal recessive forms of skeletal dysplasias. McKusick's work with the Amish population continued, with the identification of 16 new genetic syndromes that were first described in this population.…”