Two McLeod patients with novel mutations in XK

Area of Science:

• Genetics
• Neuroscience
• Hematology

Background:

• McLeod syndrome (MLS) is a rare, X-linked, late-onset disorder affecting hematological, brain, and neuromuscular systems.
• It is caused by mutations in the XK gene, leading to defective or absent XK protein.
• Acanthocytosis (abnormal red blood cell shape) is a characteristic feature.

Observation:

• This study reports on two patients with typical clinical manifestations of MLS.
• Novel mutations in the XK gene were identified in both patients.
• Patient 1 had a single base insertion (605insA) causing a frame shift.
• Patient 2 had a single base substitution in the 3' splice sequence of intron 2 (IVS2-2a>g).

Findings:

• Both identified mutations resulted in the complete absence of XK protein.
• Western blot analysis confirmed the absence of XK protein and its complex with Kell protein.

Implications:

• These findings expand the spectrum of known XK mutations associated with McLeod syndrome.
• Understanding these novel mutations aids in diagnosing and potentially managing MLS.
• Further research into the XK protein's function and its interaction with Kell protein is warranted.