Related Experiment Video
Updated: Jun 13, 2026
Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA)
Published on: August 21, 2016
Genetic Screening of Patients With Inherited Fanconi Syndrome
Yuta Inoki1, Nana Sakakibara1, Asahi Yamamoto1,2
1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Introduction:
The clinical and genetic spectrum of inherited Fanconi renotubular syndrome (FRTS) remains incompletely characterized, and the role of recently recognized genes such as GATM has not been systematically assessed.
Methods:
This retrospective study included 20 families with FRTS (14 pediatric and 6 adult index cases) who underwent targeted panel sequencing between 2016 and 2024. The variant spectrum and clinical characteristics were evaluated. Previously reported cases were reviewed to elucidate the phenotypic spectrum and renal prognosis in patients with GATM variants.
Results:
Pathogenic variants were identified in 13 of 20 index cases (65%; 4 pediatric, 9 adult cases). Disease-causing genes detected included GATM (n = 7), CLCN5 (n = 2), HNF4A (n = 1), BCS1L (n = 1), CTNS (n = 1), and EHHADH (n = 1). Notably, 4 of the 7 GATM variants were completely novel, and 2 others were first reported by our group. The review, incorporating our cases, revealed that patients with GATM variants frequently exhibited incomplete FRTS, expanding the known clinical spectrum. Kidney function exhibited progressive decline, with combined analyses of our cohort and published cases indicating a median kidney survival age of 51.9 years, establishing GATM-associated FRTS as progressive tubulopathy.
Conclusion:
Over half of the patients with primary FRTS displayed detectable monogenic etiologies, with GATM variants being unexpectedly prevalent. Our findings provide new insights into the genetic and clinical spectrum of FRTS with GATM variants, highlighting its under-recognition, phenotypic variability, and progressive kidney dysfunction. GATM variants should be considered in patients with incomplete proximal tubular abnormalities or unexplained chronic kidney disease (CKD).
