pitx2 Deficiency Results in Abnormal Ocular and Craniofacial Development in Zebrafish

Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal-dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2ex4/5 splicing-blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition) helix of the DNA-binding homeodomain. The morphological phenotype of pitx2ex4/5 morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ∼6–8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2ex4/5 morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates

Longitudinal psychological assessment in tetralogy of Fallot

To determine whether preoperative psychological testing in children with cyanotic heart disease could provide an accurate estimate of adult performance, we studied 21 subjects (mean age, 30.3±4.8 years) who had undergone surgical repair for tetralogy of Fallot between 1958 and 1966 (mean age, 8.7±3.9 years); 17 received childhood preoperative testing (mean age, 8.9±4.2) and four had early postoperative testing. Follow-up psychological tests administered in 1983 included Wechsler Adult Intelligence Scale Revised, Jackson Personality Research Form E, Rosenberg Self-Esteem Scale, and a questionnaire-interview on educational, occupational, and psychosocial status. Adult IQ ( x =93.4±15.6) and child IQ ( x =97.5±14.6) scores were highly correlated ( r =0.87, p <0.01), revealing considerable stability across 22.3±2.2 years. On 17 of 22 Jackson personality scales, the subjects (S) were within the normal range. Scoring below the 16th percentile were 11/21 S on intellectual curiosity, 9/21 S on adaptability to change, and 8/21 S on leadership skills. Scoring above the 84th percentile were 8/21 S on harm avoidance and 8/21 S on giving nurturance to others. Univariate one-way ANOVAs indicated that those subjects with the higher IQ scores had the higher incomes, job levels, and educational attainments. We conclude that the results of perioperative psychological testing in children with tetralogy of Fallot are congruent with postoperative adult intellectual and psychosocial status.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48097/1/246_2005_Article_BF02081676.pd