A Patient with neonatal cholestasis

Area of Science:

• Genetics
• Metabolic Disorders
• Neurology

Background:

• McCune-Albright syndrome is a rare genetic disorder.
• Charcot-Marie-Tooth neuropathy is a group of inherited disorders.
• Gilbert syndrome is a common liver condition.

Purpose of the Study:

• To investigate the genetic basis of polyostotic fibrous dysplasia, Charcot-Marie-Tooth neuropathy, and amino acid level abnormalities in a patient and his family.
• To identify novel genetic variants contributing to these conditions.

Main Methods:

• Clinical examination and genetic analysis of the patient and his family members.
• Whole exome sequencing to identify pathogenic variants.
• Biochemical analysis of plasma amino acid levels.

Main Results:

• The patient presented with McCune-Albright syndrome, Charcot-Marie-Tooth neuropathy due to a DNM2 mutation, and Gilbert syndrome.
• A novel pathogenic SLC7A2 variant was identified in the patient and affected family members, correlating with increased plasma arginine and lysine levels.

Conclusions:

• The study highlights a novel SLC7A2 variant as a likely cause of familial hyperargininemia and hyperlysinemia.
• Genetic factors play a significant role in the complex phenotype observed in this family, including neurological and metabolic manifestations.