PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation

Abstract

Congenital aniridia is due to deletions and point mutations in the PAX6 gene. We describe here a case of a mother and her two sons with a syndrome comprising congenital aniridia, ptosis, and slight mental retardation. The sons also show behavioral changes. The possibility of deletion around the PAX6 locus was excluded by polymorphism studies and fluorescence in situ hybridization analysis. Mutation screening of the PAX6 gene revealed the presence of a transversion C719A, resulting in the substitution of arginine for serine at residue 119. We suggest that this missense mutation is responsible both for aniridia and ptosis, and possibly also for the observed cognitive dysfunction in this family.

Selective Cortical Layering Abnormalities and Behavioral Deficits in Cortex-Specific Pax6 Knock-Out Mice

“…Notably, however, recent results from manganese-induced MRI signal enhancement analysis suggest that the pyramidal cells in Pax6cKO mice function normally (Boretius et al, 2009). These findings are in agreement with MRI results for aniridia patients, who show learning disabilities (Heyman et al, 1999;Malandrini et al, 2001) and exhibit local excesses of gray-matter volume in the hippocampus and occipital cortex, areas that are usually activated by verbal executive tasks (Ellison-Wright et al, 2004). It is worth noting that the septohippocampal connections were severely disorganized in Emx1-Cre/Pax6cKO mice and showed a decreased manganese-induced MRI signal enhancement, implying a functional deficit (Boretius at al., 2009).…”

“…The most important cognitive deficit of aniridia patients is related to impairment of the frontal lobe development (Heyman et al, 1999;Malandrini et al, 2001;Ellison-Wright et al, 2004). Aniridia probands show a deficiency in verbal tests that requires an active inhibition controlled by the prefrontal cortex (Heyman et al, 1999;Thompson et al, 2004;Bamiou et al, 2007a).…”

Aniridia

“…16 Behavioural difficulties and developmental delay are rare. 17,18 Hearing Aniridics may have central auditory processing deficits owing to abnormal interhemispheric transfer, which can cause hearing difficulties. Diagnosis requires detailed audiological assessment, but is important in patients, especially children, who already have a visual impairment.…”

Pax6 3′ deletion results in aniridia, autism and mental retardation

“…It is well known that PAX6 influences development of the nervous system and brain through regulation of proneural genes such as neurogenin 2 (Ngn2) and achaete-scute complex homolog-like 1 (Mash-1) (van Heyningen and Williamson 2002;Scardigli et al (2003). In human populations, recent studies have identified individuals with PAX6 mutations who present only with mental retardation and aniridia (Malandrini et al 2001;Ticho et al (2006;Graziano et al (2007). MRI studies of patients with aniridia and no obvious intellectual deficits have shown subtle brain abnormalities including a lack of the anterior commisure and pineal gland (Mitchell et al 2003).…”