SIX6 gene

Overview

Gene (OMIM No.)	SIX6 (#606326)
Function of gene/protein	Protein: SIX homeobox 6 Regulates other genes by binding to specific DNA regions (transcription factor) Important for initiation of eye development
Clinical phenotype (OMIM phenotype no.)	Optic disc anomalies with retinal and/or macular dystrophy (#212550)
Inheritance	Autosomal recessive
Ocular features	Microphthalmia, anophthalmia, coloboma (MAC) spectrum Horizontal nystagmus Retinal dystrophy Macular atrophy Peripapillary atrophy Small dysplastic optic discs
Systemic features	Midline defects (absence of optic chiasm, optic tracts, geniculate bodies and pituitary glands) have been reported in patients with chromosomal deletions involving SIX6 Pituitary abnormalities have been replicated in an animal model
Key investigations	B-scan USS to measure axial length to document microphthalmia Electrophysiology OCT and FAF MRI brain and orbit 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 Supportive management Systemic Multidisciplinary input may be needed due to early onset visual loss
Therapies under research	None at present
Further information	OMIM

Aldahmesh MA, Khan AO, Hijazi H, Alkuraya FS. Homozygous truncation of SIX6 causes complex microphthalmia in humans. Clin Genet. 2013;84(2):198‐199
Boucher CA, Winchester CL, Hamilton GM, Winter AD, Johnson KJ, Bailey ME. Structure, mapping and expression of the human gene encoding the homeodomain protein, SIX2. Gene. 2000;247(1-2):145‐151
Yariz KO, Sakalar YB, Jin X, et al. A homozygous SIX6 mutation is associated with optic disc anomalies and macular atrophy and reduces retinal ganglion cell differentiation. Clin Genet. 2015;87(2):192‐195
Bennett CP, Betts DR, Seller MJ. Deletion 14q (q22q23) associated with anophthalmia, absent pituitary, and other abnormalities. J Med Genet. 1991;28(4):280-281
Gallardo ME, Rodríguez De Córdoba S, Schneider AS, Dwyer MA, Ayuso C, Bovolenta P. Analysis of the developmental SIX6 homeobox gene in patients with anophthalmia/microphthalmia. Am J Med Genet A. 2004;129A(1):92-94
Ahmad ME, Dada R, Dada T, Kucheria K. 14q(22) deletion in a familial case of anophthalmia with polydactyly. Am J Med Genet A. 2003;120A(1):117-122
Li X, Perissi V, Liu F, Rose DW, Rosenfeld MG. Tissue-specific regulation of retinal and pituitary precursor cell proliferation. Science. 2002;297(5584):1180-1183

Updated on November 30, 2020

Was this article helpful?