Variability of retinopathy consequent upon novel mutations in LAMA1

Area of Science:

• Genetics
• Ophthalmology
• Neurology

Background:

• Poretti-Boltshauser Syndrome (PTBHS) is a rare, non-progressive cerebellar dysplasia disorder.
• It is caused by bi-allelic mutations in the LAMA1 gene (OMIM # 150320).
• Ophthalmic manifestations include oculomotor apraxia, high myopia, and retinal dystrophy, with limited variants previously reported.

Purpose of the Study:

• To describe novel LAMA1 variants in two unrelated families.
• To detail the specific retinal structural and functional manifestations associated with LAMA1 deficiency.

Main Methods:

• Whole-genome sequencing was performed on affected individuals from two families.
• Clinical evaluations included comprehensive ophthalmic examinations, retinal imaging (color, autofluorescence, OCT, fluorescein angiography), and electroretinography.

Main Results:

• Two novel LAMA1 frameshift variants and one deletion were identified.
• Patients exhibited a spectrum of retinal abnormalities, including retinopathy, abnormal vascularization, myopia, and oculomotor apraxia.
• Variability in severity of retinal dystrophy and vascular development was observed.

Conclusions:

• LAMA1 deficiency leads to significant and variable retinal structural and functional consequences.
• The findings highlight both retinal dystrophy and abnormal retinal vascularization as key features of LAMA1-related disorders.
• This study expands the known spectrum of LAMA1 variants and their associated phenotypes.