CMA increased detection rates and had a shorter turnaround time; therefore, late amniocentesis may serve as an extremely helpful tool for detecting abnormalities or reassuring parents following late appearing abnormal sonographic findings. However, CMA may expose uncertain findings for which the couple should be pre-counselled. The procedure appears safe. This article is protected by copyright. All rights reserved.

Four isozymes of steroid 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) encoded by different loci catalyze the reversible conversion of androstenedione to testosterone and that of estrone to estradiol. The 17 beta HSD type 3 (17 beta HSD3) isozyme is encoded by the 17 beta HSD3 gene on chromosome 9q22 and expressed only in testes. Inherited defects in the 17 beta HSD3 isozyme cause a form of male pseudohermaphroditism that is rare within the general population, but frequent among a highly inbred Arab population in the Gaza strip. A point mutation in exon 3, codon 80 of the 17 beta HSD3 gene, R80Q, caused by a single base substitution from CGG to CAG was identified in both alleles of 24 individuals from 9 extended Arab families from Gaza, Jerusalem, and Lod-Ramle. Twenty-one homozygotes were male pseudohermaphrodites (46,XY) with testicular 17 beta HSD3 deficiency, born with either female-looking external genitalia or various degrees of genital ambiguity. If not reassigned in infancy, they were reared as females until puberty, when marked virilization occurred, often leading to the spontaneous adoption of a male gender role. In contrast, the 3 homozygote females (46,XX) were asymptomatic, had normal internal and external genitalia and normal sexual development, and revealed no biochemical evidence of 17 beta HSD3 deficiency. The molecular pattern in these families is compatible with an autosomal recessive mode of inheritance that is sex dependent.

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Most X-linked diseases show a recessive pattern of inheritance in which female carriers are unaffected. In X-linked retinitis pigmentosa (XLRP), however, both recessive and semi-dominant inheritance patterns have been reported. We identified an Israeli family with semi-dominant XLRP due to a missense mutation (p.G275S) in the RPGR gene. The mutation was previously reported in two Danish families with recessive XLRP. Obligate carriers from the two Danish families had no visual complaints and normal to slightly reduced retinal function, while those from the Israeli family suffered from high myopia, low visual acuity, constricted visual fields, and severely reduced electroretinogram (ERG) amplitudes. The disease-related RPGR haplotype of the Israeli family was found to be different from the one found in the two Danish families, indicating that the mutation arose twice independently on different X-chromosome backgrounds. A series of genetic analyses excluded skewed X-inactivation pattern, chromosomal abnormalities, distorted RPGR expression level, and mutations in candidate genes as the cause for the differences in disease severity of female carriers. To the best of our knowledge, this is the first detailed analysis of an identical mutation causing either a recessive or a semi-dominant X-linked pattern of disease in different families. Our results indicate that an additional gene (or genes), linked to RPGR, modulate disease expression in severely affected carriers. These may be related to the high myopia concomitantly found in affected carriers from the Israeli family.

Forty-two fetuses with non-homologous Robertsonian translocations were analyzed for uniparental disomy (UPD). One fetus with a de novo translocation t(13q;14q) had maternal isodisomy of chromosome 14. In a summary of the published data (including the present study), 315 cases were analyzed for UPD after prenatal diagnosis of balanced Robertsonian translocations, of these two fetuses had UPD, giving a risk estimate of 0.65% (CI 0.2-2.3). This risk justifies the recommendation of UPD analysis in fetuses diagnosed prenatally with Robertsonian translocations, with the emphasis on the chromosomes known to contain imprinted genes, such as 14 and 15. We also discuss the possibility of UPD in offspring of Robertsonian translocation carriers with normal karyotype. Based on the risk for UPD in fetuses with Robertsonian translocation we suggest to test these fetuses for UPD and to do so on amniocytes rather than chorionic villi when the risk for unbalanced karyotype is approximately 1%, comparable to the risk for UPD.