Infantile glaucoma in Down's syndrome (trisomy 21)

We examined five patients with Down's syndrome and bilateral infantile glaucoma. In the first few months of life four patients had large cloudy corneas, breaks in Descemet's membrane, increased intraocular pressure, photophobia, and tearing. In one patient the diagnosis was delayed until 3 1/2 years of age because of concomitant nasolacrimal duct obstruction. Two patients developed cataracts and retinal detachment and have undergone multiple surgical procedures. The clinical course in these two older patients suggests that coexistence of congenital glaucoma, severe myopia, and cataracts in patients with trisomy 21 strongly predisposes for the development of retinal detachment and poor visual outcome.     

Ocular histopathologic characteristics of cobalamin C type vitamin B12 defect with methylmalonic aciduria and homocystinuria.

The eyes of a 22-month-old girl with the cobalamin C complementation type of combined methylmalonic aciduria and homocystinuria were studied with light and electron microscopy. We observed vacuolization of the iris pigment epithelium, loss of photoreceptors in the central 3.3 mm of the macula, partial loss of the nerve fiber and ganglion cell layers between the fovea and optic disk, and partial optic atrophy. The sclera in the posterior pole was thickened with deposition of mucopolysaccharide. Electron microscopy showed inclusions containing fine granular material in conjunctival fibrocytes; corneal epithelium, keratocytes, and endothelial cells; iris pigment epithelium; ganglion cells; retinal pigment epithelium; and choroid and scleral fibrocytes. Enlarged mitochondria and clear vacuoles distended the corneal endothelial cells. We found evidence of possible lysosomal dysfunction and mucopolysaccharide storage, as well as a clinicopathologic correlation of the macular degeneration in this disease.     

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability in the Rat

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability inthe Rat. SHU, H., TEITELBAUM, T., WEBB, A. S., MARPLE, L., BRUNCK,B. DEI ROSSI, D., MURRAY, J., AND PAUSTENBACH, D. (1988). Fundam.Appl. Toxicol. 10, 335-343. 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD), an unwanted by-product formed during the manufactureof hexachlorophene and phenoxyherbicides, has been found asan environmental contaminant in many U.S. and Western Europeansites. This study examines in the rat the degree of dermal absorptionof TCDD bound to soil. Such information would assist regulatoryagencies in evaluating the degree of exposure of humans whocome in contact with TCDD-contaminated soil. Several parameterswhich may influence dermal absorption were studied, includingTCDD dose, duration of contact, presence of crankcase oil asa co-contaminant, and environmentally contaminated vs laboratory-preparedsoil. The dermal penetration of TCDD following 4 hr of contactwith skin was approximately 60% of that following 24 hr of contact(P 0.05). Following 24 hr of contact with the skin, the degreeof dermal uptake of TCDD contaminated soil was approximately1% of the administered dose. Under the conditions of the presentstudy, the degree of uptake does not appear to be influencedto any significant extent by the concentration of TCDD on soil,the presence of crankcase oil as co-contaminants, or by environmentallyvs laboratory-contaminated soil. Although a number of parametersexamined in this study did not significantly influence the degreeof dermal absorption of TCDD in the rat following 24 hr of contactwith the contaminated soil, the unqualified use of the 1% valueto estimate human exposure would overestimate human exposure,since there is general agreement among researchers that ratskin tends to be more permeable than human skin to highly lipid-solublecompounds such as TCDD.     

Intergenerational instability of the CAG repeat of the gene for Machado- Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter- allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.      

Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs

In this study, we evaluated the effect of low level occupationalexposure of nurses in a medical oncology unit in Cairo, Egypt,to anticancer drugs. Twenty nurses who constantly handled thesedrugs and 20 controls, matched according to age and sex, wereexamined. Metaphase chromosomes were studied. Percentages ofmetaphases with chromosomal aberrations were significantly higher(P < 0.001) in the exposed group (6.1 ± 2.7) versusthe controls (2.6 ± 1.6). The detected chromosomal aberrationswere in the form of chromatid gaps, chromatid breaks and acentricfragments. Micronucleated peripheral blood lymphocytes werealso analyzed in cytochalasin B treated binucleated lymphocytes.There was significant increase in cells with micronuclei (P< 0.001) in nurses (10.05 ± 4.71) in comparison tothe matched control (5.42 ± 2.22) (P < 0.001). Nursesexposed to the cytotoxic drugs for     

Bilateral microphthalmia with cyst,facial clefts,and limb anomalies: a new syndrome with features of Waardenburg syndrome,cerebro-oculo-nasal syndrome,and craniotelencephalic dysplasia

We report a patient with bilateral microphthalmia with cyst, limb anomalies, and multiple facial malformations. This patient has clinical features similar to Waardenburg ophthalmo-acromelic syndrome, cerebro-oculo-nasal syndrome, and craniotelencephalic dysplasia. Although all of these syndromes are characterized by microphthalmia, the presently reported patient does not have the complete pattern of any of these syndromes, It is possible that he has a previously undescribed syndrome, most closely related to the cerebro-oculo-nasal syndrome with malformations outside the craniofacial region. More case reports are needed to further delineate this possibly new syndrome.     

The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region

We have recently reported isolation of the gene responsible for X- linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.      

Confirmation of the autosomal recessive syndrome of ectopia lentis and distinctive craniofacial appearance

We report four members of a Lebanese Druze family with the syndrome of lens dislocation, spontaneous filtering blebs, anterior segment abnormalities, and a distinctive facial appearance. The constellation of clinical abnormalities in these patients is not suggestive of the Marfan syndrome or other connective tissue disorders associated with ectopia lentis. We previously described this syndrome in another presumably unrelated and highly inbred Druze family from the mountains of Lebanon. We postulated autosomal recessive inheritance in a pseudo-dominant pedigree. A few isolated reports of similar cases are scattered in the world literature. We now confirm that this is a distinct autosomal recessive syndrome whose gene mutation is enriched in the Lebanese Druze community.