Recent advances in CGG repeat diseases and a proposal of fragile X-associated tremor/ataxia syndrome, neuronal intranuclear inclusion disease, and oculophryngodistal myopathy (FNOP) spectrum disorder

• Published in: Journal of human genetics 2023-03, Vol.68 (3), p.169-174
• Main Authors: Ishiura, Hiroyuki, Tsuji, Shoji, Toda, Tatsushi
• Format: Article
• Language: English
• Subjects: Ataxia; Ataxia - genetics; Disease; Epilepsy; Families & family life; Females; Fragile X Mental Retardation Protein - genetics; Fragile X syndrome; Fragile X Syndrome - genetics; Genomes; Genotype & phenotype; Humans; Intellectual disabilities; Males; Muscular Dystrophies - genetics; Mutation; Myoclonus; Myopathy; Ovaries; Phenotypes; Review; Tremor; Tremor - genetics; Trinucleotide Repeat Expansion; Whole genome sequencing
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-022-01116-y

While whole genome sequencing and long-read sequencing have become widely available, more and more focuses are on noncoding expanded repeats. Indeed, more than half of noncoding repeat expansions related to diseases have been identified in the five years. An exciting aspect of the progress in this field is an identification of a phenomenon called repeat motif-phenotype correlation. Repeat motif-phenotype correlation in noncoding repeat expansion diseases is first found in benign adult familial myoclonus epilepsy. The concept is extended in the research of CGG repeat expansion diseases. In this review, we focus on newly identified CGG repeat expansion diseases, update the concept of repeat motif-phenotype correlation in CGG repeat expansion diseases, and propose a clinical concept of FNOP (fragile X-associated tremor/ataxia syndrome, neuronal intranuclear inclusion disease, and oculopharyngodistal myopathy)-spectrum disorder, which shares clinical features and thus probably share some common disease pathophysiology, to further facilitate discussion and progress in this field.