L1CAM mutation in a boy with hydrocephalus and duplex kidneys

Area of Science:

• Genetics
• Developmental Biology
• Neurology

Background:

• L1CAM gene mutations are linked to L1-spectrum diseases, affecting neurological development.
• L1CAM is expressed in developing kidneys, and mouse models show renal malformations.
• However, L1CAM mutations have not been previously associated with renal anomalies in humans.

Observation:

• A boy presented with hydrocephalus, agenesis of the corpus callosum, and other L1-spectrum disease features.
• He also exhibited bilateral duplex kidneys with a unilateral mega-ureter and hydronephrotic upper pole.
• Genetic testing revealed a novel 2 bp deletion in the L1CAM gene.

Findings:

• The patient's L1CAM mutation resulted in a truncated or absent protein.
• Despite significant renal malformations, the patient maintained normal renal function at age 9.
• This case links L1CAM mutations to renal abnormalities in humans, mirroring findings in L1cam-deficient mice.

Implications:

• L1CAM mutations should be considered in patients with unexplained renal malformations.
• This expands the phenotypic spectrum associated with L1CAM mutations.
• L1CAM is a potential candidate gene for congenital kidney and urinary tract anomalies.