Human Ring Chromosomes: A Practical Guide for Clinicians and Families

This book presents chromosome-wise clinical cases following an evidence-based protocol, in addition to providing the scientific background on the mechanisms of human ring chromosome (RC) formation. Presence of RCs in a genome can lead to several rare genetic diseases. This book, edited by the leading experts Prof. Peining Li and Prof. Thomas Liehr, is the first comprehensive book on this topic.

Over the past 60 years, banding cytogenetics, fluorescence in situ hybridization, chromosome microarray analysis, and whole genome sequencing have been used to diagnose cases with a RC. Ring syndrome of sever growth retardation and variable intellectual disability has been considered a common clinical feature for all RCs. Clinical heterogeneity of chromosome-specific deletion and duplication syndromes, gene-related organ and tissue defects, cancer predisposition to different types of tumors, and reproduction failure has been reported in the literature. However, the cases of RCs reportedin the literature account for less than 1% of its real occurrence. Current diagnostic practice lacks laboratory standards for analyzing cellular behavior and genomic imbalances of RCs to evaluate its compound effects on patients. The under-representation of clinical cases and the lack of comprehensive diagnostic analysis make challenging to establish accurate clinico-cytogenomic correlations. Given recent advances in genomic technology and organized efforts from peer experts, standardized cytogenomic diagnosis and evidence-based clinical management could be envisioned for all patients with RCs.

Furthermore, supernumerary small ring chromosomes and the patient’s perspective are addressed—the latter by including family stories of RC-carrier relatives. Acquired RCs in various cancers are also discussed, as well as the potential role of RCs in research applications like iPSC cellular modeling and genomic editing.

This book is a valuable reference for clinical geneticists, personnel in cytogenetics and molecular genetics laboratories, genetic counselors, and researchers in related fields.

Peining Li is Professor in the Department of Genetics at Yale School of Medicine. He received a Bachelor of Science degree in Biology from Nankai University and a PhD in Medical Genetics from University of Alabama at Birmingham. He was Assistant Professor in the Department of Pediatrics at Washington University School of Medicine in St. Louis until he joined Yale in 2005. He has been the director of Yale Clinical Cytogenetics Laboratory which provides karyotyping, fluorescent in situ hybridization (FISH), and chromosome microarray analysis (CMA) to detect chromosomal abnormalities and pathogenic copy number variants (pCNVs) for prenatal, pediatric, and cancer patients from Yale New Haven Hospital and other affiliated hospitals and clinics. His research activities focus on the characterization of genomic structure and gene function from human chromosome abnormalities to identify disease-causing genes or markers of diagnostic value and mechanistic insights. He has published around 100 peer-reviewed articles, book chapters, and review papers in the fields of clinical cytogenetics and molecular genetics. He has been active members of the American Board of Medical Genetics and Genomics, American College of Medical Genetics and Genomics, and American Society of Human Genetics, and the organizer of the International Consortium for Human Ring Chromosomes (ICHRC).

Prof. Thomas Liehr is working in human genetics since 1991. He is biologist by education and head of the molecular cytogenetic group in Jena, Germany. Research fields include clinical genetics, leukemia cytogenetics and interphase structure of human chromosomes. The results of his research are published in ~15 books, >110 book chapter, >840 referred papers, and ~900 abstracts. His particular expertise includes small supernumerary marker chromosomes (sSMC), chromosomal heteromorphisms and uniparental disomy – see ChromosOmics databases. He is active member of the European Board of Medical Genetics and received multiple prices, two invited professorships and a Dr.h.c.