+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RAX and anophthalmia in humans: evidence of brain anomalies

RAX and anophthalmia in humans: evidence of brain anomalies

Molecular Vision 18(): 1449-1456

To report the clinical and genetic study of two families of Egyptian origin with clinical anophthalmia. To further determine the role of the retina and anterior neural fold homeobox gene (RAX) in anophthalmia and associated cerebral malformations. Three patients with clinical anophthalmia and first-degree relatives from two consanguineous families of Egyptian origin underwent full ophthalmologic, general and neurologic examination, and blood tests. Cerebral magnetic resonance imaging (MRI) was performed in the index cases of both families. Genomic DNA was prepared from venous leukocytes, and direct sequencing of all the exons and intron-exon junctions of RAX was performed after PCR amplification. Clinical bilateral anophthalmia was observed in all three patients. General and neurologic examinations were normal; obesity and delay in psychomotor development were observed in the isolated case. Orbital MRI showed a hypoplastic orbit with present but rudimentary extraocular muscles and normal lacrimal glands. Cerebral MRI showed agenesis of the optic nerves, optic tracts, and optic chiasma. In the index case of family A, the absence of the frontal and sphenoidal sinuses was also noted. In the index case of family B, only the sphenoidal sinus was absent, and there was significant cortical atrophy. The three patients carried a novel homozygous c.543+3A>G mutation (IVS2+3A>G) in RAX. Parents were healthy heterozygous carriers. No mutations were detected in orthodenticle homeobox 2 (OTX2), ventral anterior homeobox 1 (VAX1), or sex determining region Y-box 2 (SOX2). This is the first report of a homozygous splicing RAX mutation associated with autosomal recessive bilateral anophthalmia. To our knowledge, only two isolated cases of anophthalmia, three null and one missense case affecting nuclear localization or the DNA-binding homeodomain, have been found to be caused by compound heterozygote RAX mutations. A novel missense RAX mutation was identified in three patients with bilateral anophthalmia and a distinct systemic and neurologic phenotype. The mutation potentially affects splicing of the last exon and is thought to result in a protein that has an aberrant homeodomain and no paired-tail domain. Functional consequences of this change still need to be characterized.

(PDF emailed within 1 workday: $29.90)

Accession: 055333526

Download citation: RISBibTeXText

PMID: 22736936

Related references

SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies. American Journal of Medical Genetics. Part A 138a(2): 95-98, 2005

Anophthalmia, cleft lip/palate, facial anomalies, and CNS anomalies and hypothalamic disorder in a newborn: a midline developmental field defect. American Journal of Medical Genetics 50(1): 39-41, 1994

Bilateral nasal proboscis associated with unilateral anophthalmia, unilateral diffuse pigmentation of the conjunctiva, and anomalies of the skull and brain. A.M.A. Archives of Otolaryngology 70: 545-550, 1959

Anophthalmia-limb anomalies. Ryoikibetsu Shokogun Shirizu: 202-203, 2001

SOX2 anophthalmia syndrome and dental anomalies. American Journal of Medical Genetics. Part A 167a(11): 2830-2833, 2016

Anophthalmia, esophageal atresia and genital anomalies Three new cases. American Journal of Human Genetics 73(5): 296, November, 2003

Bilateral anophthalmia associated with further anomalies of the head in German Holstein calves. Dtw. Deutsche Tierarztliche Wochenschrift 110(11): 454-456, 2003

Anophthalmia and microphthalmia in the Alberta Congenital Anomalies Surveillance System. Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie 40(1): 38-44, 2005

A novel heterozygous SOX2 mutation causing anophthalmia/microphthalmia with genital anomalies. European Journal of Medical Genetics 52(4): 273-276, 2009

Congenital anophthalmia with caudal vertebral anomalies in Japanese Brown cattle. Journal of Veterinary Medical Science 57(4): 693-696, 1995

Are specific eye findings a useful predictor of the presence of associated major anomalies in anophthalmia/microphthalmia?. American Journal of Human Genetics 67(4 Supplement 2): 138, October, 2000

Clinical anophthalmia, dextrocardia, and skeletal anomalies in an infant born to consanguineous parents. American Journal of Medical Genetics 37(2): 178-181, 1990

Mechanism of radiation anencephaly, anophthalmia, and pituitary anomalies; repair in the mammalian embryo. A.M.A. Archives of Pathology 57(5): 363-378, 1954

Profound microphthalmia clinical anophthalmia without associated anomalies and with normal intelligence in a large arab kindred. American Journal of Human Genetics 41(3 SUPPL): A71, 1987

Deletion at 14q22-23 indicates a contiguous gene syndrome comprising anophthalmia, pituitary hypoplasia, and ear anomalies. American Journal of Medical Genetics. Part A 140(16): 1711-1718, 2006