GDF6 gene

Overview
Microphthalmia, anophthalmia, coloboma (MAC)
References

Overview

Gene (OMIM No.)	GDF6 (#601147)
Function of gene/protein	Protein: growth differentiation factor 6 Part of the TGFβ superfamily Involved in regulating growth and maturation of bone, cartilage and the retina Regulates apoptosis during photoreceptor development
Clinical phenotype (OMIM phenotype no.)	Klippel-Feil syndrome 1, autosomal dominant (#118100) LCA/EOSRD: Leber congenital amaurosis 17 (#615360) Microphthalmia with coloboma 6, digenic (#613703) Microphthalmia, isolated 4 (#613094) Multiple synostoses syndrome 4 (#617898)
Inheritance	Autosomal dominant in most cases Autosomal recessive in a patient diagnosed with LCA
Ocular features	Microphthalmia, anophthalmia, coloboma (MAC) spectrum Foveal hypoplasia Extinguished ERG recordings and poor vision from birth in a patient with compound heterozygous mutation
Systemic features	Klippel-Feil syndrome (verterbral segmentation defects leading to a fused appearance) Other skeletal anomalies (malformed ossicles, post-axial polydactyly, hemivertebrae, rib malformations) Craniofacial (hemifacial hypoplasia, cleft lip and palate) Genital anomalies (phimosis and single testis)
Key investigations	B-scan USS to measure axial length to document microphthalmia Electrophysiology MRI brain and orbit Spine X-ray Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosis	Next generation sequencing Targeted gene panels (MAC) Whole genome sequencing
Management	Ocular Management of MAC Systemic Multidisciplinary approach
Therapies under research	None at present
Further information	Medline Plus

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References

Asai-Coakwell M, French CR, Ye M, et al. Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. Hum Mol Genet. 2009;18(6):1110‐1121
Asai-Coakwell M, March L, Dai XH, et al. Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. Hum Mol Genet. 2013;22(7):1432‐1442
Tassabehji M, Fang ZM, Hilton EN, et al. Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. Hum Mutat. 2008;29(8):1017‐1027
Wang J, Yu T, Wang Z, et al. A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal. J Bone Miner Res. 2016;31(4):882‐889
Zhang L, Lim SL, Du H, et al. High temperature requirement factor A1 (HTRA1) gene regulates angiogenesis through transforming growth factor-β family member growth differentiation factor 6. J Biol Chem. 2012;287(2):1520‐1526
Gonzalez-Rodriguez J, Pelcastre EL, Tovilla-Canales JL, et al. Mutational screening of CHX10, GDF6, OTX2, RAX and SOX2 genes in 50 unrelated microphthalmia-anophthalmia-coloboma (MAC) spectrum cases. Br J Ophthalmol. 2010;94(8):1100‐1104
den Hollander AI, Biyanwila J, Kovach P, et al. Genetic defects of GDF6 in the zebrafish out of sight mutant and in human eye developmental anomalies. BMC Genet. 2010;11:102

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Updated on November 30, 2020

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