Novel mutations in ALDH1A3 associated with autosomal recessive anophthalmia/microphthalmia, and review of the literature
S Lin, GV Harlalka, A Hameed, HM Reham… - BMC medical …, 2018 - Springer
BMC medical genetics, 2018•Springer
Background Autosomal recessive anophthalmia and microphthalmia are rare
developmental eye defects occurring during early fetal development. Syndromic and non-
syndromic forms of anophthalmia and microphthalmia demonstrate extensive genetic and
allelic heterogeneity. To date, disease mutations have been identified in 29 causative genes
associated with anophthalmia and microphthalmia, with autosomal dominant, autosomal
recessive and X-linked inheritance patterns described. Biallelic ALDH1A3 gene variants are …
developmental eye defects occurring during early fetal development. Syndromic and non-
syndromic forms of anophthalmia and microphthalmia demonstrate extensive genetic and
allelic heterogeneity. To date, disease mutations have been identified in 29 causative genes
associated with anophthalmia and microphthalmia, with autosomal dominant, autosomal
recessive and X-linked inheritance patterns described. Biallelic ALDH1A3 gene variants are …
Background
Autosomal recessive anophthalmia and microphthalmia are rare developmental eye defects occurring during early fetal development. Syndromic and non-syndromic forms of anophthalmia and microphthalmia demonstrate extensive genetic and allelic heterogeneity. To date, disease mutations have been identified in 29 causative genes associated with anophthalmia and microphthalmia, with autosomal dominant, autosomal recessive and X-linked inheritance patterns described. Biallelic ALDH1A3 gene variants are the leading genetic causes of autosomal recessive anophthalmia and microphthalmia in countries with frequent parental consanguinity.
Methods
This study describes genetic investigations in two consanguineous Pakistani families with a total of seven affected individuals with bilateral non-syndromic clinical anophthalmia.
Results
Using whole exome and Sanger sequencing, we identified two novel homozygous ALDH1A3 sequence variants as likely responsible for the condition in each family; missense mutation [NM_000693.3:c.1240G > C, p.Gly414Arg; Chr15:101447332G > C (GRCh37)] in exon 11 (family 1), and, a frameshift mutation [NM_000693.3:c.172dup, p.Glu58Glyfs*5; Chr15:101425544dup (GRCh37)] in exon 2 predicted to result in protein truncation (family 2).
Conclusions
This study expands the molecular spectrum of pathogenic ALDH1A3 variants associated with anophthalmia and microphthalmia, and provides further insight of the key role of the ALDH1A3 in human eye development.
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