Two Novel Variants in the ATRX Gene Associated with Variable Phenotypes

Area of Science:

• Genetics
• Molecular Biology
• Clinical Medicine

Background:

• X-linked alpha-thalassemia mental retardation (ATR-X) syndrome is a rare genetic disorder.
• Mutations in the ATRX gene on the X chromosome cause ATR-X syndrome.
• The syndrome presents with a range of intellectual disabilities and physical features.

Observation:

• Two unrelated patients of Sri Lankan origin were studied.
• Novel missense variants, c.839C>T|p.Cys280Tyr and c.5369C>T|p.Ala1790Val, in the ATRX gene were identified in these patients.
• The patients exhibited variable phenotypes resembling X-linked mental retardation-hypotonic facies syndrome and Smith-Fineman-Myers syndrome.

Findings:

• The identified ATRX variants are novel.
• These variants were associated with diverse clinical presentations within the ATR-X syndrome spectrum.
• The findings highlight genetic heterogeneity in ATR-X syndrome.

Implications:

• This study expands the clinical and genetic spectrum of ATR-X syndrome.
• It provides new opportunities for molecular diagnosis of ATRX mutations.
• Early and accurate diagnosis can facilitate better patient management for severe global developmental delay and intellectual disabilities.