Single-Gene Disorders and Mendelian Diseases

DOI 10.66715/cerebral/2026.singlegd | Cerebral Publication Private Limited | CIN: U58111DL2025PTC459104 | 2026 | Volume 1 | Issue 2 | Page 1-300 | ISBN: 978-81-689463-0-9 | Book Title: - Textbook of Clinical Genetics | Chapter-5: Single-Gene Disorders and Mendelian Diseases

Author: Dr. Abhilash Sahoo, MBBS (Hons), MD Paediatrics, Department of Paediatrics, SRTR GMC, Ambajogai

Abstract

Single-gene disorders, also known as Mendelian diseases, are inherited conditions caused by pathogenic variants in a single gene and follow predictable patterns of inheritance. Although individually rare, these disorders collectively affect millions of people worldwide and contribute significantly to morbidity, mortality, and healthcare burden. Understanding the molecular basis and inheritance patterns of Mendelian diseases is fundamental to clinical genetics, enabling accurate diagnosis, genetic counseling, risk assessment, and the development of targeted therapeutic strategies. Advances in molecular diagnostics and genomic technologies have greatly enhanced the identification of disease-causing variants, allowing earlier diagnosis and improved patient management.

This chapter introduces the principles of Mendelian inheritance, including autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial inheritance. It explores the molecular mechanisms responsible for single-gene disorders, such as point mutations, insertions, deletions, splice-site variants, repeat expansions, and loss- or gain-of-function mutations. Representative disorders—including cystic fibrosis, sickle cell disease, β-thalassemia, Huntington disease, Duchenne muscular dystrophy, Marfan syndrome, phenylketonuria, hemophilia, and fragile X syndrome—are discussed with emphasis on their genetic basis, clinical manifestations, diagnostic approaches, and management.

The chapter also reviews modern diagnostic techniques such as polymerase chain reaction (PCR), Sanger sequencing, next-generation sequencing (NGS), whole-exome sequencing (WES), and whole-genome sequencing (WGS), highlighting their roles in confirming diagnoses and guiding precision medicine. Emerging therapeutic approaches, including gene therapy, genome editing, RNA-based treatments, enzyme replacement therapy, and personalized medicine, are examined alongside ethical considerations related to predictive testing, carrier screening, reproductive counseling, and informed consent.

A comprehensive understanding of single-gene disorders and Mendelian diseases equips healthcare professionals, researchers, and students with the knowledge required to interpret genetic information, provide effective patient care, and integrate genomic advances into clinical practice, ultimately improving diagnosis, treatment, and long-term health outcomes in the era of precision medicine.