Cytogenetic studies have shown that 40-60% of patients with Ullrich-Turner syndrome (UTS) are 45,X, whereas the rest have structural aberrations of the X chromosome or mosaicism with a second cell line containing a structurally normal or abnormal X or Y chromosome. However, molecular analysis has demonstrated a higher proportion of mosaicism, and studies in different populations have shown an extremely variable frequency of Y mosaicism of 0-61%. We used Southern blot analysis and polymerase chain reaction (PCR) to detect the presence of Ycen, ZFY, SRY, and Yqh in 50 Mexican patients with UTS and different karyotypes to determine the origin of marker chromosomes and the presence of Y sequences. Our results indicated the origin of the marker chromosome in 1 patient and detected the presence of Y sequences in 4 45,X patients. Taken together, we found a 12% incidence of Y sequences in individuals with UTS. The amount of Y-derived material was variable, making the correlation between phenotype and molecular data difficult. Only 1 patient had a gonadoblastoma. We discuss the presence of Y chromosomes or Y sequences in patients with UTS and compare our frequency with that previously reported.
The 19q13.11 microdeletion syndrome (MIM613026) is a clinically recognisable condition in which a 324-kb minimal overlapping critical region has been recently described. However, genes not included within this region, such as WTIP and UBA2, have been proposed to contribute to the clinical characteristics observed in patients. Using cytogenetic techniques, single nucleotide polymorphism arrays, and the quantitative polymerase chain reaction, we identified a novel case with a 2.49-Mb deletion derived from a de novo chromosomal rearrangement. Based on a review of the literature, we support the notion that UBA2 haploinsufficiency could contribute to the phenotype of this rare genomic disorder. UBA2 belongs to a protein complex with sumoylation activity, and several transcription factors, hormone receptors, and signalling proteins related to brain and sexual development are regulated by this post-translational modification. Additional clinical reports and further research on UBA2 molecular function are warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-014-0061-z) contains supplementary material, which is available to authorized users.
Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies. Partial duplication of chromosome 3q syndrome is a well-described condition, and the phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation. Approximately 60%–75% of cases are derived from a balanced translocation. We describe a family with a pure typical partial trisomy 3q syndrome derived from a maternal balanced translocation t(3;13)(q26.2;p11.2). As the chromosomal rearrangement involves the short arm of an acrocentric chromosome, the phenotype corresponds to a pure trisomy 3q26.2-qter syndrome. There are 4 affected individuals and several carriers among three generations. The report of this family is relevant because there are few cases of pure duplication 3q syndrome reported, and the cases described here contribute to define the phenotype associated with the syndrome. Furthermore, we confirmed that the survival until adulthood is possible. This report also identified the presence of glycosaminoglycans in urine in this family, not related to the chromosomal abnormality or the phenotype.
Turner syndrome is a chromosomal disorder in which all or part of one X chromosome is missing. The meiotic or mitotic origin of most cases remains unknown due to the difficulty in detecting hidden mosaicism and to the lack of meiotic segregation studies. We analyzed 15 Turner patients, 10 with a 45,X whereas the rest had a second cell line with abnormal X-chromosomes: a pseudodicentric, an isochromosome, one large and one small ring, and the last with a long arm deletion. Our aims were: to detect X cryptic mosaicism in patients with a 45,X constitution; to determine the parental origin of the abnormality; to infer the zygotic origin of the karyotype and to suggest the timing and mechanism of the error(s) leading to the formation of abnormal X chromosomes from maternal origin. Molecular investigation did not revealed heterozygosity for any microsatellite, excluding X mosaicism in the 45,X cases. Parental origin of the single X chromosome was maternal in 90% of these patients. Three of the structurally abnormal Xs were maternally derived whereas the other two were paternal. These results allowed us to corroborate breakpoints in these abnormal X chromosomes and suggest that the pseudodicentric chromosome originated from post-zygotic sister chromatid exchange, whereas the Xq deleted chromosome probably arose after a recombination event during maternal meiosis.
46,XX maleness is characterized by the presence of testicular development in subjects who lack a Y chromosome. The majority of affected persons have normal external genitalia, but 10–15% show various degrees of hypospadias. Several hypotheses have been proposed to explain the etiology of this constitution: translocation of the testis‐determining factor (TDF) from the Y to the X chromosome, mutation in an autosomal or X chromosomal gene which permits testicular determination in the absence of TDF, and undetected mosaicism with a Y‐bearing cell line. We report the pheno‐typic data and results of molecular analyses performed in six sporadic Mexican males with 46,XX karyotype. Molecular studies revealed Yp sequences in two individuals (ZFY+SRY+) with different phenotypes, a third one presented with a smaller segment of Yp (ZFY–SRY+) and complete virilization, while the remaining three were Y‐negative and showed hypospadias. In all subjects a hidden mosaicism with a Y‐bearing cell line was ruled out due to the absence of Y‐centromeric sequences. Our data demonstrate that the phenotype does not always correlate with the presence or absence of Y‐sequences in the genome, and confirm that 46,XX maleness is a genetically heterogeneous condition.
The Nance-Horan syndrome is an X-linked disorder characterized by congenital cataract, facial features, microcornea, microphthalmia, and dental anomalies; most of the cases are due to NHS gene mutations on Xp22.13. Heterozygous carrier females generally present less severe features, and up to 30% of the affected males have intellectual disability. We describe two patients, mother and daughter, manifesting Nance-Horan syndrome. The cytogenetic and molecular analyses demonstrated a 46,X,t(X;1)(p22.13;q22) karyotype in each of them. No copy-number genomic imbalances were detected by high-density microarray analysis. The mother had a preferential inactivation of the normal X chromosome; expression analysis did not detect any mRNA isoform of NHS. This is the first report of Nance-Horan syndrome due to a skewed X chromosome inactivation resulting from a balanced translocation t(X;1) that disrupts the NHS gene expression, with important implications for clinical presentation and genetic counseling.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.