Developmental defects

SUMOl haploinsufficiency has been linlced to a developmental defect Based on the finding that a patient with a cleft lip and palate had a mutation in the SUMOl gene locus, a mouse model was generated that had reduced SUMOl expression. Increased frequency for a cleft palate or oblique facial cleft was observed in the transgenic mice, suggesting that SUMO haploinsufficiency can lead to developmental defects. 

Concreteness Inability to think in abstract terms. It may be a primary developmental defect or secondary to organic mental disorder or schizophrenia. 

Other homeobox gene targeting experiments have resulted in more dramatic developmental defects. Homozygous //ox-1.5 null mutants showed a number of alterations (Chisaka and Capecchi, 1991). The mice died at or shortly after birth, apparently from circulation and/or pulmonary problems. These animals showed hypertrophy of the atria and... 

Chisaka, O., and Capecchi. M. R. (1991). Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature 350 413-419. 

The answer is B. While all of the listed conditions are consistent with lethargy and developmental defects, the lactic acidosis rules out pyruvate kinase deficiency. Thiamine and niacin deficiencies are unlikely due to the lack of effect of vitamin supplementation. Excess pyruvate is the source of the elevated alanine in the serum. The clinical findings are thus consistent with pyruvate carboxylase deficiency, which is associated with severe hypoglycemia due to fasting due to impaired gluconeogenesis. 

Turner s syndrome is a genetic defect that affects females (sufferers carry only one of the usual two X chromosomes). These individuals are infertile, often show developmental defects, mental retardation and short stature. Virtually all clinical trials involving Turner s syndrome patients confirm that administration of GH significantly increases growth velocity, indicating its therapeutic usefulness in these cases. 

Most drugs and chemicals pose a threat to the developing fetus. An estimated 4 to 5% of developmental defects in humans result from prenatal exposure to drugs or environmental chemicals. This is particularly important, since women with irregular menstrual cycles may be exposed to teratogens and enter the sensitive period of organogenesis before pregnancy is suspected. 

Warfarin readily crosses the placenta. It can cause hemorrhage at any time during pregnancy as well as developmental defects when administered during the first trimester. Therefore, venous thromboembolic disease in pregnant women is generally treated with heparin, best administered by subcutaneous injection. 

Twelve or more additional triplet repeat diseases, many with neurological symptoms, have been identified (Table 26-4).405 407a These involve other trinucleotide repeats 5 -(GCG) , 5 -(CTG) , 5 -(GAA) , and 5 -(CAG) . In synpolydactyly, an inherited developmental defect causing malformation of hands and feet, an expansion of a GCG trinucleotide occurs within the gene HoxD 13. This results in incorporation of a polyalanine tract near the N terminus of the protein.408 Myotonic dystrophy DM1 (Box 19-A) results from expansion of CTG to 6 kbp or more within the untranslated 3 region of a gene for cAMP-dependent protein kinase.405 The mRNA transcripts accumulate... 

Alaluusua S, Lukinmaa P-L, Vartiainen T, et al. 1996. Polychlorinated dibenzo-p-dioxins and dibenzofurans via mother s milk may cause developmental defects in the child s teeth. Environ Toxicol Pharmacol 1 193-197. 

Definitive evidence that dihydrotestosterone (DHT) is a potent androgen with its own important physiological and pathophysiological actions, separate from those of testosterone, was provided by two reports in 1974 of a rare inborn disorder of male phenotypic sexual differentiation caused by a deficiency in 5a-reductase, the enzyme that converts testosterone to DHT. The reduction in the conversion of testosterone to DHT by 5a-reductase, which underlies this syndrome, leads to a specific developmental defect in the formation of the male external genitalia and the prostate. Males with this genetic disorder exhibit a striking phenotype, in which the internal genitalia are normal... 

Matt N, Ghyselinck NB, Wendling O, Chambon P, Mark M (2003) Retinoic acid-induced developmental defects are mediated by RARb/RXR heterodimers in the pharyngeal endoderm. Development, 130 2083-2093. 

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