Fig. 1

Genetic analysis of three patients from two unrelated Chinese families with autosomal recessive spastic ataxia of Charlevoix-Saguenay. (A) The family tree of Family 1. (B) The family tree of Family 2. (C) For Patient #1, the calves were pseudohypertrophic. (D) Sanger sequencing results confirmed that Patients #1 (II1) and #2 (II2) were hemizygous for c.8310_8313delAGAT (p.Asp2771fs4*) in SACS (black arrow), the mother (I2) wild type, and the father (I1) heterozygous. (E) Copy number variant analysis of the whole-exome sequencing (WES) data revealed a large chromosome 13 deletion in Patient #1. X-axis: the position on the chromosome corresponding to the region of variation currently displayed. Y-axis: ratio of target sample reads per kilobase per million mapped reads (RPKM) value to the mean value of background library RPKM. (F) Overview of the low-coverage whole-genome sequencing (WGS) of Patient #1. The red arrow indicates the region with abnormal copy numbers in Patient #1. (G) Low-coverage WGS result of chromosome 13 in Patient #2. The red arrow shows the chr13q12.12 deletion. (H) Sanger sequencing results confirmed that Patient #3 (II1) was heterozygous for 2881 C > T (p.Arg961*) in SACS (black arrow), the little brother (II2) wild type, the mother (I2) wild type, and the father (I1) heterozygous. (I) Sanger sequencing results confirmed that Patient #3 (II1) was heterozygous for 6409 C > T (p.Gln2137*) in SACS (black arrow), the little brother (II2) wild type, the mother (I2) heterozygous, and the father (I1) wild type. (J) For Patient #3, brain magnetic resonance angiography conducted on October 4, 2022, revealed the typical linear “tigroid” T2 hypointense stripes in the pons. (K) For Patient #3, thoracic spine magnetic resonance imaging on October 8, 2022, revealed a thin thoracic spinal cord.