BACKGROUND: High myopia with alopecia areata in the occipital region has been 
observed in patients with Knobloch syndrome caused by COL18A1 mutations. This 
study investigated other possible genetic causes of high myopia in patients with 
alopecia areata in the cranial midline.
METHODS: Six patients with early onset high myopia and alopecia areata in the 
cranial midline were recruited. Targeted high-throughput sequencing was 
performed on the proband's DNA to detect potential pathogenic variants. 
Cosegregation analysis was performed for available family members. Minigene 
assay and RNA Sequencing were used to validate the abnormality of possible 
splicing change and gross deletion. Ophthalmological and neuroimaging 
examinations were performed.
RESULTS: Eight novel and one known loss-of-function mutants were detected in all 
six patients, including a gross deletion detected by RNA sequencing. Four 
COL18A1 mutants in three patients with scalp leisure in the occipital region; 
and five LAMA1 mutations in three patients with scalp leisure in the parietal 
region. Further assessments indicated that patients with COL18A1 mutations had 
Knobloch syndrome, and the patients with LAMA1 mutations had Poretti-Boltshauser 
syndrome.
CONCLUSION: Our study found that early onset high myopia with midline alopecia 
areata could be caused not only by mutations of the COL18A1 gene but also by 
mutations in the LAMA1 gene. To our knowledge, we are the first to observe scalp 
defects in patients with LAMA1 mutations. High myopia with alopecia areata in 
the cranial midline could be treated as an early diagnostic clue for 
ophthalmologists to consider the two kinds of rare diseases.