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Panfeng Wang, Xueshan Xiao, Shiqiang Li, Xiaoyun Jia, Qingjiong Zhang; High myopia with alopecia areata in cranial midline：COL18A1 and LAMA1 mutant. Invest. Ophthalmol. Vis. Sci. 2019;60(9):391.
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© ARVO (1962-2015); The Authors (2016-present)
Investigate the genetic causes of high myopia in patients with alopecia areata in cranial midline
Patients with high myopia and alopecia areata in cranial midline were recruited. Comprehensive eye and skull examinations were performed. Genomic DNA was prepared form venous leukocytes. Exome sequencing was conducted, and potential pathogenic variants were filtered according to the ACMG guideline after using multistep bioinformatics analyses. Co-segregation analysis was performed among available family members.
A total of 4 unrelated male patients with average age of 4.94 ± 1.89 years were recruited. Potential pathogenic compound heterozygous mutations in LAMA1 gene, c.1487dup (p.(Asn496Lysfs*15))and c.4579C>T ( p.(Gln1527*))as well as c. 6151 C>T (p.(Arg2051*))and c.1494_1504del (p.(Gly499Valfs*8)), were found in two patients. Potential pathogenic homozygous mutations in COL18A1 gene, c.3545-29_3550del and c.4290_4299del(p.(Gly1431Glufs*9)), were found in other two patients. The average refractive error was -10.92±-1.83 and the best corrected vision was less than 0.3. Strabismus and nystagmus were noticed in all four patients. Besides typical high myopia fundus liking Leopard pattern, dysplasia of the papilla and macular degeneration were observed. Extra bone spicule accumulation and loss of pigmentation around it could be seen in the middle and periphery of the temporal fundus. ERG indicates a severe decrease in cone and rod cell. The skin thickened in alopecia areata. In patients with LAMA1 mutation, alopecia areata appeared in the midline of parietal region, and MRI indicated cerebellar dysplasia and obvious enlargement of the fourth ventricle. In patients with COL18A1 gene mutation, alopecia areata appeared in the midline of occipital region, and MRI showed no obvious abnormalities in the brain.
COL18A1 is causative gene for Knobloch syndrome characterized by typical eye abnormalities with occipital skull defects. LAMA1 is causative gene for Poretti - Boltshauser syndrome characterized by typical cerebellar dysplasia with eye abnormalities. Our study found that high myopia with midline alopecia areata could not only be caused by mutations of COL18A1 gene, but also be caused by mutations of LAMA1 gene. Further examination should be taken especially in high myopia children with alopecia areata in cranial midline at eye clinics.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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