X-linked intellectual disability type Nascimento is a clinically distinct, probably underdiagnosed entity

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Molecular Biology

Background:

• X-linked intellectual disability type Nascimento is linked to UBE2A gene mutations.
• The condition is characterized by specific craniofacial dysmorphism, skin anomalies, and intellectual disability.
• Previous reports documented limited familial point mutations and deletions involving UBE2A.

Purpose of the Study:

• To report additional individuals with UBE2A-associated intellectual disability.
• To further delineate the clinical phenotype and genetic spectrum of Nascimento intellectual disability.
• To investigate the X-inactivation patterns in carrier females.

Main Methods:

• Genetic analysis of eight individuals from five families with suspected UBE2A-associated intellectual disability.
• Identification of mutations including small deletions, missense, and nonsense mutations in UBE2A.
• Analysis of X-inactivation patterns in carrier females.

Main Results:

• Eight new cases of UBE2A-associated intellectual disability were identified, including small deletions, missense, and nonsense mutations.
• All affected males exhibited the characteristic clinical phenotype.
• Carrier females with familial UBE2A aberrations showed completely skewed X inactivation and were clinically unaffected.

Conclusions:

• X-linked intellectual disability type Nascimento is a distinct, potentially underdiagnosed entity.
• Clinically unaffected carrier females with skewed X inactivation require careful genetic counseling.
• Array analysis requires careful checking for resolution to detect small deletions, or alternative methods should be used.