Co-occurrence of Charcot-Marie-Tooth disease type 1 and glomerulosclerosis in a patient with a de novo INF2 variant

Abstract

Background Renal disease is associated with Charcot-Marie-Tooth disease (CMT), a common inherited neurological disorder. Three forms of CMT have been identified: CMT1 of the demyelinating type, CMT2 of the axonal defect type, and intermediate type (Int-CMT). INF2 is an important target for variants that cause the complex symptoms of focal segmental glomerulosclerosis (FSGS) and CMT. Case presentation We report the case of a 13-year-old female Chinese patient (born in 2011) with a rare co-occurrence of CMT1 and glomerulosclerosis (GS) (CMT1-GS). The patient presented with slowly progressive gait disorder with unsteadiness during walking, pes cavus, and kyphoscoliosis since the age of 1 year. Electrophysiological studies and brain magnetic resonance imaging revealed demyelinating features consistent with CMT1. At 12 years of age, she was hospitalised for hypertension and dizziness; her serum albumin was 27.9 g/L, serum creatinine was 87 μmol/L, estimated glomerular filtration rate was 88.6 mL/min, and 24-h urine protein was 4.95 g. A renal biopsy showed glomerulosclerosis. Renal function deteriorated further during the follow-up period, and she received a kidney transplant at the age of 13. Whole-exome sequencing identified a de novo heterozygous c.326T > G (p.Met109Arg) variant in exon 2 of INF2 . The variant was classified as “pathogenic” according to the American College of Medical Genetics and Genomics criteria. Conclusions We describe a rare clinical phenotype of CMT1-GS associated with a de novo variant of INF2 . Our findings expand the phenotypic and genotypic spectrums of INF2 -associated disorders. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-024-03891-6.