Pituitary function and glucose tolerance in a family with a PAX6 mutation

Hergott-Faure, Lucie; Borot, Sophie; Kleinclauss, C.; Abitbol, Marc; Penfornis, A.

doi:10.1016/j.ando.2012.10.001

Cited by 12 publications

(8 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hergott et al reported data on detailed pituitary studies using the stimulation testing of five PAX6 mutation carriers (10). In this paper, they found no clear pituitary deficiencies other than subtle corticotrope deficiency.…”

Section: Discussionmentioning

confidence: 75%

See 1 more Smart Citation

Heterozygous defects in PAX6 gene and congenital hypopituitarism

Takagi

Nagasaki

Fujiwara

et al. 2015

European Journal of Endocrinology

View full text Add to dashboard Cite

Background: The prevalence of congenital hypopituitarism (CH) attributable to known transcription factor mutations appears to be rare and other causative genes for CH remain to be identified. Due to the sporadic occurrence of CH, de novo chromosomal rearrangements could be one of the molecular mechanisms participating in its etiology, especially in syndromic cases. Objective: To identify the role of copy number variations (CNVs) in the etiology of CH and to identify novel genes implicated in CH. Subjects and methods: We enrolled 88 (syndromic: 30; non-syndromic: 58) Japanese CH patients. We performed an array comparative genomic hybridization screening in the 30 syndromic CH patients. For all the 88 patients, we analyzed PAX6 by PCR-based sequencing. Results: We identified one heterozygous 310-kb deletion of the PAX6 enhancer region in one patient showing isolated GH deficiency (IGHD), cleft palate, and optic disc cupping. We also identified one heterozygous 6.5-Mb deletion encompassing OTX2 in a patient with bilateral anophthalmia and multiple pituitary hormone deficiency. We identified a novel PAX6 mutation, namely p.N116S in one non-syndromic CH patient showing IGHD. The p.N116S PAX6 was associated with an impairment of the transactivation capacities of the PAX6-binding elements. Conclusions: This study showed that heterozygous PAX6 mutations are associated with CH patients. PAX6 mutations may be associated with diverse clinical features ranging from severely impaired ocular and pituitary development to apparently normal phenotype. Overall, this study identified causative CNVs with a possible role in the etiology of CH in !10% of syndromic CH patients.

show abstract

Section: Discussionmentioning

confidence: 75%

“…Recently two papers have been published, showing that PAX6 mutations may be associated with impaired pituitary function (10,11). Hergott et al reported data on detailed pituitary studies using the stimulation testing of five PAX6 mutation carriers (10).…”

Section: Discussionmentioning

confidence: 99%

Heterozygous defects in PAX6 gene and congenital hypopituitarism

Takagi

Nagasaki

Fujiwara

et al. 2015

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…The fact that PAX6 is a regulator of the early differentiation of somatotroph, lactotroph and thyrotroph cells made it a good candidate in patients with eye defects and pituitary deficiency. This has been reported in patients with an unexpected phenotype: five patients from the same large family, with heterozygous PAX6 mutations and eye anomalies, were indeed presenting with isolated partial corticotroph deficiency, but normal GH, PRL and TSH functions (17). For the first time, Takagi et al identified PAX6 anomalies in two patients with GH deficiency.…”

Section: Novel Aetiologies Involving Actors Known To Be Associated Wimentioning

confidence: 89%

MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency

Castinetti¹,

Reynaud²,

Saveanu³

et al. 2016

European Journal of Endocrinology

View full text Add to dashboard Cite

Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes of inheritance for alterations of genes encoding transcription factors have also been described. Finally, actors known to be involved in a very specific phenotype (hypogonadotroph hypogonadism for instance) have been identified in a wider range of phenotypes. These data thus suggest that new mechanisms could explain the low rate of aetiological identification in this heterogeneous group of diseases. Taking into account the fact that several reviews have been published in recent years on classical aetiologies of CPHD such as mutations of POU1F1 or PROP1, we focused the present overview on the data published in the last 5 years, to provide the reader with an updated review on this rapidly evolving field of knowledge.

show abstract

“…In addition to its role in ocular development, PAX6 has been shown to regulate pancreatic islet cell development [58,59]. The clinical implications of PAX6 mutations on glucose tolerance are unclear as published studies include few patients and show conflicting results [60,61]. In our study, only 1 patient had a history of type 1 diabetes, while the remainder of the individuals had no history of glucose intolerance.…”

Section: Discussionmentioning

confidence: 63%

Phenotypic variation in a four-generation family with aniridia carrying a novel PAX6 mutation

Wang¹,

Prasov²,

Richards³

et al. 2017

Journal of American Association for Pediatric Ophthalmology and

View full text Add to dashboard Cite

Aniridia is a congenital disease that affects almost all eye structures and is primarily caused by loss-of-function mutations in the PAX6 gene. The degree of vision loss in aniridia varies and is dependent on the extent of foveal, iris, and optic nerve hypoplasia and the presence of glaucoma, cataracts, and corneal opacification. Here, we describe a 4-generation family in which 7 individuals across 2 generations carry a novel disease-causing frameshift mutation (NM_000280.4(PAX6):c.565TC>T) in PAX6. This mutation results in an early stop codon in exon 8, which is predicted to cause nonsense-mediated decay of the truncated mRNA and a functionally null PAX6 allele. Family members with aniridia showed differences in multiple eye phenotypes including iris and optic nerve hypoplasia, congenital and acquired corneal opacification, glaucoma, and strabismus. Visual acuity ranged from 20/100 to less than 20/800. Patients who required surgical intervention for glaucoma or corneal opacification had worse visual outcomes. Our results show that family members carrying a novel PAX6 frameshift mutation have variable expressivity, leading to different ocular comorbidities and visual outcomes.

show abstract

Pituitary function and glucose tolerance in a family with a PAX6 mutation

Cited by 12 publications

References 11 publications

Heterozygous defects in PAX6 gene and congenital hypopituitarism

Heterozygous defects in PAX6 gene and congenital hypopituitarism

MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency

Phenotypic variation in a four-generation family with aniridia carrying a novel PAX6 mutation

Contact Info

Product

Resources

About