Infantile-onset CMT2D/dSMA-V in a Chinese family with parental germline mosaicism for a novel mutation in the GARS1 gene

Background and aims: Both Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are GARS1 disease phenotypes involving axonal peripheral neuropathy. Patients often develop clinical symptoms in their teens. Herein, we reported a Chinese family with infantile-onset CMT2D/dSMA-V.

Methods: Clinical evaluation and laboratory examination were performed in our proband, the older sister from this family, and trio exome sequencing (ES) was conducted on the proband and her parents, followed by Sanger sequencing.

Results: A novel GARS1 mutation (c.997G>C, p.E333Q; NM_002047) was identified in this patient and her younger sister but not in her parents; thus, it is presumed that this mutation is inherited from a germline mosaic parent. The younger sister began to exhibit weakness of her hands and feet at the age of 1 year old.

Conclusion: This is the first report of infantile CMT2D/dSMA-V in China. Our study increases the number of infantile-onset cases, as well as reported pathogenic variants in the GARS1 gene, and highlights the important role of exome sequencing in the clinical diagnosis of disease and enabling subsequent prenatal diagnosis. Our study reminds us to consider the possibility of parent germline mosaicism in the subsequent prenatal genetic diagnosis when identifying a de novo variant.