Asai-Coakwell et al. (2013) studied a female LCA patient with compound heterozygous mutations in the GDF6 gene (see MOLECULAR GENETICS) who had vision limited to detection of hand motions, with an extinguished electroretinogram (ERG) typical of the LCA ... Asai-Coakwell et al. (2013) studied a female LCA patient with compound heterozygous mutations in the GDF6 gene (see MOLECULAR GENETICS) who had vision limited to detection of hand motions, with an extinguished electroretinogram (ERG) typical of the LCA phenotype. She did not have other ocular or systemic phenotypes, but the authors noted that she had not undergone radiologic imaging to detect milder GDF6-induced skeletal disease. Evaluation of her clinically unaffected mother revealed a delayed rod b-wave implicit time on ERG; similarly, her apparently unaffected father showed reduced b-wave amplitude.
Asai-Coakwell et al. (2013) analyzed the GDF6 gene in 279 DNA samples from patients diagnosed with Leber congenital amaurosis or juvenile retinitis pigmentosa (JRP) who were negative for mutation in known causative genes, and identified compound heterozygosity for ... Asai-Coakwell et al. (2013) analyzed the GDF6 gene in 279 DNA samples from patients diagnosed with Leber congenital amaurosis or juvenile retinitis pigmentosa (JRP) who were negative for mutation in known causative genes, and identified compound heterozygosity for 2 missense mutations in 1 female LCA proband: A249E (601147.0001) and D57H (601147.0008). The A249E mutation had previously been identified in a family with Klippel-Feil syndrome (118100), in 1 proband with isolated microphthalmia (MCOP4; 613094), and in a patient with coloboma and postaxial polydactyly without vertebral defects. Heterozygosity for GDF6 missense mutations was identified in 3 probands from the LCA/JRP cohort: A249E, A199T (601147.0007), and E292D (601147.0009). Asai-Coakwell et al. (2013) hypothesized that a second variant in the TGF-beta (see 190180) pathway was present in the probands with a heterozygous GDF6 mutation, but exome sequencing yielded incomplete coverage across open-reading frames of BMP (see 112261) ligands, preventing identification of known heterozygous mutations.