PAX6 molecular analysis and genotype–phenotype correlations in families with aniridia from Australasia and Southeast Asia

Creative Commons Attribution-NonCommercial-NoDerivatives License 3.0, or CC BY-NC-ND 3.0 (see http://creativecommons.org/licenses/by-nc-nd/3.0/ for license terms)Purpose Aniridia is a congenital disorder caused by variants in the PAX6 gene. In this study, we assessed the involvement of PAX6 in patients with aniridia from Australasia and Southeast Asia. Methods Twenty-nine individuals with aniridia from 18 families originating from Australia, New Caledonia, Cambodia, Sri Lanka, and Bhutan were included. The PAX6 gene was investigated for sequence variants and analyzed for deletions with multiplex ligation-dependent probe amplification. Results We identified 11 sequence variants and six chromosomal deletions, including one in mosaic. Four deleterious sequence variants were novel: p.(Pro81HisfsTer12), p.(Gln274Ter), p.(Ile29Thr), and p.(Met1?). Ocular complications were associated with a progressive loss of visual function as shown by a visual acuity ≤ 1.00 logMAR reported in 65% of eyes. The prevalence of keratopathy was statistically significantly higher in the Australasian cohort (78.6%) compared with the Southeast Asian cohort (9.1%, p=0.002). Variants resulting in protein truncating codons displayed limited genotype–phenotype correlations compared with other variants. Conclusions PAX6 variants and deletions were identified in 94% of patients with aniridia from Australasia and Southeast Asia. This study is the first report of aniridia and variations in PAX6 in individuals from Cambodia, Sri Lanka, Bhutan, and New Caledonia, and the largest cohort from Australia

PAX6 molecular analysis and genotype–phenotype correlations in families with aniridia from Australasia and Southeast Asia

Creative Commons Attribution-NonCommercial-NoDerivatives License 3.0, or CC BY-NC-ND 3.0 (see http://creativecommons.org/licenses/by-nc-nd/3.0/ for license terms)Purpose Aniridia is a congenital disorder caused by variants in the PAX6 gene. In this study, we assessed the involvement of PAX6 in patients with aniridia from Australasia and Southeast Asia. Methods Twenty-nine individuals with aniridia from 18 families originating from Australia, New Caledonia, Cambodia, Sri Lanka, and Bhutan were included. The PAX6 gene was investigated for sequence variants and analyzed for deletions with multiplex ligation-dependent probe amplification. Results We identified 11 sequence variants and six chromosomal deletions, including one in mosaic. Four deleterious sequence variants were novel: p.(Pro81HisfsTer12), p.(Gln274Ter), p.(Ile29Thr), and p.(Met1?). Ocular complications were associated with a progressive loss of visual function as shown by a visual acuity ≤ 1.00 logMAR reported in 65% of eyes. The prevalence of keratopathy was statistically significantly higher in the Australasian cohort (78.6%) compared with the Southeast Asian cohort (9.1%, p=0.002). Variants resulting in protein truncating codons displayed limited genotype–phenotype correlations compared with other variants. Conclusions PAX6 variants and deletions were identified in 94% of patients with aniridia from Australasia and Southeast Asia. This study is the first report of aniridia and variations in PAX6 in individuals from Cambodia, Sri Lanka, Bhutan, and New Caledonia, and the largest cohort from Australia

The Exstrophy-epispadias complex

Exstrophy-epispadias complex (EEC) represents a spectrum of genitourinary malformations ranging in severity from epispadias (E) to classical bladder exstrophy (CEB) and exstrophy of the cloaca (EC). Depending on severity, EEC may involve the urinary system, musculoskeletal system, pelvis, pelvic floor, abdominal wall, genitalia, and sometimes the spine and anus. Prevalence at birth for the whole spectrum is reported at 1/10,000, ranging from 1/30,000 for CEB to 1/200,000 for EC, with an overall greater proportion of affected males. EEC is characterized by a visible defect of the lower abdominal wall, either with an evaginated bladder plate (CEB), or with an open urethral plate in males or a cleft in females (E). In CE, two exstrophied hemibladders, as well as omphalocele, an imperforate anus and spinal defects, can be seen after birth. EEC results from mechanical disruption or enlargement of the cloacal membrane; the timing of the rupture determines the severity of the malformation. The underlying cause remains unknown: both genetic and environmental factors are likely to play a role in the etiology of EEC. Diagnosis at birth is made on the basis of the clinical presentation but EEC may be detected prenatally by ultrasound from repeated non-visualization of a normally filled fetal bladder. Counseling should be provided to parents but, due to a favorable outcome, termination of the pregnancy is no longer recommended. Management is primarily surgical, with the main aims of obtaining secure abdominal wall closure, achieving urinary continence with preservation of renal function, and, finally, adequate cosmetic and functional genital reconstruction. Several methods for bladder reconstruction with creation of an outlet resistance during the newborn period are favored worldwide. Removal of the bladder template with complete urinary diversion to a rectal reservoir can be an alternative. After reconstructive surgery of the bladder, continence rates of about 80% are expected during childhood. Additional surgery might be needed to optimize bladder storage and emptying function. In cases of final reconstruction failure, urinary diversion should be undertaken. In puberty, genital and reproductive function are important issues. Psychosocial and psychosexual outcome depend on long-term multidisciplinary care to facilitate an adequate quality of life

AUSTRALIAN AND NEW ZEALAND STUDY OF PHOTODYNAMIC THERAPY IN CHOROIDAL AMELANOTIC MELANOMA

Purpose: To evaluate the safety and efficacy of primary photodynamic therapy (PDT) for posterior choroidal amelanotic melanomas. Methods: Patients with posterior choroidal amelanotic melanomas up to 6 mm in height were treated with PDT using verteporfin as the photosensitizing agent. Treatment was repeated every 3 months until the tumor was flat up to a maximum of 6 treatments. Tumor response and recurrence was assessed by clinical examination, photography, and ultrasonography. Patients were monitored 3 monthly for a minimum of 3 years. Results: Thirty-six of 41 (88%) patients had complete regression after an initial course of PDT. Of them, 20 (56%) had no recurrence, 3 (8%) had recurrences that were successfully treated with further PDT, and 13 (36%) had recurrences that failed or were not amenable to further PDT. None of the measured baseline characteristics predicted treatment outcomes. There was no reduction in visual acuity due to PDT. The mean follow-up time was 3.5 years. Conclusion: In this large series, primary PDT was highly effective in achieving initial regression of posterior choroidal amelanotic melanomas. Photodynamic therapy is a vision-preserving treatment option for these tumors; however, patients need to be followed up closely because there is a significant rate of recurrence

Successful treatment of a large choroidal abscess in an immunocompetent child

Background We report the case of a systemically well 4-year-old Aboriginal boy who developed a choroidal abscess after being poked in the left eye with a blunt object. Case report This boy presented with redness and reduced vision in the left eye after a blunt object was poked into his eye by his sibling. He was noted to have a choroidal mass which finally manifested as a choroidal abscess. Results His initial visual acuity was 6/60, and dilated fundus examination demonstrated a localised solid-appearing choroidal elevation involving the posterior pole, including the macula. An ultrasound of the eye revealed a choroidal haematoma with an atypical appearance, whose height was 8 mm with a base of 12 mm × 10 mm. The lesion failed to resolve, and eventually resulted in orbital cellulitis that did not respond to intravenous and topical antibiotic treatment. He then went on to achieve complete visual recovery after successful management by transcleral incision, drainage and systemic antibiotic therapy. Conclusion Choroidal abscess has been described in patients who are debilitated, immunocompromised or suffer with systemic disease such as cystic fibrosis or endocarditis. This case represents a unique report of staphylococcal choroidal abscess in a healthy child that completely resolved after transcleral drainage and systemic antibiotics

Education policy enactment research: disrupting continuities

No abstract available