ABSTRACT
We report a case of a male fetus of 20 weeks of gestation with plurimalformed observed by transonic scan and confirmed by MR. The karyotype was 46, XY. Molecular analysis showed a microdeletion of about 100 kb in the CTNNA3 gene.
ABSTRACT
OBJECTIVE: the purpose of this paper is to report the first case of megaurethra in a fetus with Meckel syndrome and in a fetus with femal pseudoermaphroditism. RESULTS: the former case refers to a fetus of 13 weeks gestation with the three following prominent anomalies, observed by transonic scan and confirmed by autopsy: congenital megaurethra, anal atresia, single umbelical artery. The latter case refers to a fetus of 18 weeks gestation. Autopsy confirmed penile malformation and revealed ovaries in the abdomen. The karyotype was 46,XX with normal molecular karytype. The megaurethra was discovered by sonography at 18 weeks gestation. Autopsy confirmed penile malformation and revealed ovaries in the abdomen. The karyotype was 46,XX with normal molecular karyotype (Array-CGH, 1 Mb of resolution). METHODS: transonic scan, autopsy, karyotype, array-CGH. CONCLUSIONS: the first prenatal cases of two genetic syndromes with megaurethra have been reported, concening respectively a fetus with Meckel syndrome and a fetus with femal pseudoermaphroditism. The latter was confirmed by both autopsy and the normal female 46,XX karyotype.
ABSTRACT
The importance of the genetic factor in the aetiology of premature ovarian failure (POF) is emphasized by the high percentage of familial cases and X chromosome abnormalities account for 10% of chromosomal aberrations. In this study, we report the detailed analysis of 4 chromosomal abnormalities involving the X chromosome and associated with POF that were detected during a screening of 269 affected women. Conventional and molecular cytogenetics were valuable tools for locating the breakpoint regions and thus the following karyotypes were defined: 46,X,der(X)t(X;19)(p21.1;q13.42)mat, 46,X,t(X;2)(q21.33;q14.3)dn, 46,X,der(X)t(X;Y)(q26.2;q11.223)mat and 46,X,t(X;13)(q13.3;q31)dn. A bioinformatic analysis of the breakpoint regions identified putative candidate genes for ovarian failure near the breakpoint regions on the X chromosome or on autosomes that were involved in the translocation event. HS6ST1, HS6ST2 and MATER genes were identified and their functions and a literature review revealed an interesting connection to the POF phenotype. Moreover, the 19q13.32 locus is associated with the age of onset of the natural menopause. These results support the position effect of the breakpoint on flanking genes, and cytogenetic techniques, in combination with bioinformatic analysis, may help to improve what is known about this puzzling disorder and its diagnostic potential.
ABSTRACT
Mesomelic dysplasia is a severe shortening of forearms and forelegs, and is found in several distinct human syndromes. Here, we report the cloning of the breakpoints of a human t(2;8)(q31;p21) balanced translocation associated with mesomelic dysplasia of the upper limbs, as well as with vertebral defects. We show that this translocation does not disrupt any gene, hence it most likely exerts its deleterious effect by modifying gene regulation. The HOXD complex lies approximately 60 kb from the translocation breakpoint on chromosome 2. This cluster of genes has an important role in the development of both the vertebral column and the limbs. Only a few cases of mutations of these homeotic genes have been described so far in humans. However, gain- and loss-of-function of Hoxd genes in mice can induce mesomelic dysplasia-like phenotypes, suggesting that misexpression of HOXD genes may indeed be at the origin of this hereditary phenotype.