Fig. 1: Pedigree and brain imaging findings in representative cases identified by short tandem repeat (STR) analysis.

a Dentatorubral-pallidoluysian atrophy (DRPLA) was incidentally identified by STR analysis in families 1 and 2. Trio exome sequencing was conducted due to the initial observation of developmental delay in the probands. Initially, both fathers were asymptomatic; however, relevant clinical findings emerged during the follow-up periods. The pedigrees were reconstructed after genotype-phenotype correlation, confirmation of DRPLA, and cascade screening for other affected members. b Spinocerebellar ataxia type 7 (SCA7) identified in families 4 and 5. The proband and her mother from family 4 underwent exome sequencing after receiving negative results from SCA panel tests at another institution. However, ExpansionHunter suggested repeat expansions in SCA7. Subsequent fragment analysis and Cas9-mediated Nanopore long-read sequencing cross-validated that the previous results was false negative. Cascade screening of family 4 further confirmed ATXN7 repeat expansions in other family members. In family 5, ATXN7 repeat counts estimated by ExpansionHunter were 10/36 in the proband and 10/42 in his father, respectively. Subsequent fragment analysis confirmed the repeat expansions (92 and 42 repeats, respectively). c Myotonic dystrophy type 1 (DM1) identified in family 6. Despite ExpansionHunter identifying 64 and 62 repeats in the proband and his mother, respectively, Southern blotting confirmed the presence of extremely long repeats in the proband (1171 repeats) and his mother (617 repeats). During the reverse phenotyping of the mother, myotonia of the tongue and grip were noticed. Brain magnetic resonance imaging revealed cerebellar atrophy in the probands, indicated by yellow arrows. Samples that underwent exome sequencing within the families are highlighted in pink. Black arrows denote the probands within the families.