1/10. Brachytelephalangic dwarfism due to the loss of ARSE and SHOX genes resulting from an X;Y translocation.Here we report an 8-year-old male patient who had mesomelic shortening of forearms and legs, brachytelephalangia and ichthyotic skin lesions. Chromosomal analysis showed an X;Y translocation involving the short arm of the x chromosome (Xp). fluorescence in situ hybridization (FISH) and molecular studies localized the breakpoints on Xp22.3 in the immediate vicinity of the KAL gene demonstrating deletions of steroid sulfatase (STS), arylsulfatase E (ARSE), and short stature homeo box (SHOX) genes. It was suspected that the patient was suffering from chondrodysplasia punctata because of a loss of the arylsulfatase E (ARSE) gene. However, no stippled epiphyses were to be seen in the neonatal radiograph. Interestingly, this patient is the first case with a proven loss of the ARSE gene without chondrodysplasia punctata, assuming that chondrodysplasia punctata is not an obligatory sign of ARSE gene loss. Brachytelephalangia was the only result of ARSE gene deletion in this case. The patient's mother also had dwarfism and showed Madelung deformity of the forearms. She was detected as a carrier of the same aberrant x chromosome. The male patient did not show Madelung deformity, demonstrating that Lerri-Weill syndrome phenotype may be still incomplete in children with SHOX gene deletion. The wide clinical spectrum in the male and the Leri-Weill phenotype in his mother are the results of both a deletion involving several sulfatase genes in Xp22.3 and the SHOX gene located in the pseudoautosomal region. Nevertheless, there is no explanation for the absence of chondrodysplasia punctata despite the total loss of the ARSE gene. Further studies are necessary to investigate genotype/phenotype correlation in cases with translocations or microdeletions on Xp22.3, including the ARSE and the SHOX gene loci.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/10. Maternal isodisomy for 14q21-q24 in a man with diabetes mellitus.We report a 20-year-old man with maternal uniparental disomy for chromosome 14 (UPD14) and maturity-onset diabetes mellitus (DM). He had pre- and postnatal growth retardation, developed DM at age 20 years without any autoimmune antibodies, and had a mosaic 45,XY,der(14;14)(q10;q10)[129]/46,XY, 14,der(14;14)(q10;q10)[1] karyotype. Allelotyping using microsatellite markers covering the entire 14q indicated segmental maternal isodisomy for 14q21-q24 and maternal heterodisomy of the remaining regions of the chromosome. It is thus tempting to speculate that the segmental isodisomy led to reduction to homozygosity for a mutant gene and thus caused his DM, although the possibility of coincidental occurrence of the two events cannot totally be ruled out. fluorescence in situ hybridization (FISH) analysis using BAC clone probes revealed that the isodisomic segment did not overlap any known IDDM or NIDDM susceptibility loci on chromosome 14, suggesting a novel locus for a subset of DM at the isodisomic segment.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/10. An Xp; Yq translocation causing a novel contiguous gene syndrome in brothers with generalized epilepsy, ichthyosis, and attention deficits.PURPOSE: We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri-Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the x chromosome. methods: physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement. RESULTS: The subjects had generalized epilepsy, X-linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative x chromosome. Deleted distal Xp genes included short-stature homeobox on the x chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X-chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1 , KAL , STS-, SHOX-) mat. CONCLUSIONS: Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/10. Inherited ring chromosome 8 without loss of subtelomeric sequences.We report the first case of inherited ring chromosome 8 syndrome without loss of subtelomeric sequences. The proband is a 6 1/2-year-old boy with short stature, microcephaly, mild mental retardation, and behavioral problems including hyperactivity and attention deficit. His mother presented the same physical features but intelligence was normal. family history also revealed an uncle and a grandmother, with short stature and microcephaly. Moderate mental retardation was reported in the uncle. Karyotypes and fluorescence in situ hybridization (FISH) analyses were performed on peripheral blood lymphocytes for both child and mother. The child's karyotype was reported as 46,XY,r(8)(p23q24.3)[24]/45,XY,-8[2] and the mother's karyotype 46,XX,r(8)(p23q24.3)[22]/45,XX,-8[2]/47,XX,r(8)(p23q24.3), r(8)(p23q24.3)[1]. FISH studies showed no deletion of subtelomeric sequences for both child and mother indicating that no or little chromosomal euchromatic material has been deleted. These findings indicate that ring chromosome 8 without loss of subtelomeric sequences can be inherited and that carriers in a same family present with cognitive function ranging from mild mental retardation to normal intelligence.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/10. Duplication 10q confirmed by dna in situ hybridization.Partial duplication of 10q is a recognizable clinical entity. In most of the reported cases, the trisomic segment is identified by a balanced translocation state in a parent. Verification remains a problem in de novo cases. However, the recent availability of whole chromosome probes allows for confirmatory diagnosis of suspected cases. We describe a case of de novo duplication (10q) with verification using dna in situ hybridization.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
6/10. 18q- and 18q mosaicism in a mentally retarded boy.A mentally retarded boy was found to have an unusual chromosomal mosaicism [46,XY, del(18) (q22)/46,XY,iso psu dic(18)(q23)]. The clinical manifestations are compatible with the 18q- syndrome. The chromosome alteration was defined by high resolution banding and fluorescence in situ hybridization (FISH). A mechanism to explain the origin of the two cell lines is presented and discussed.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/10. Dynamic mosaicism involving an unstable supernumerary der(22) chromosome in cat eye syndrome.We have studied a girl, her sister and her mother who had a supernumerary marker chromosome in mosaicism. The marker was studied by cytogenetic methods and non-isotopic in situ hybridization with the single D22S9 dna probe which maps to 22q11. The supernumerary chromosome was derived from a chromosome 22 and it did not present the same morphology in all the cells. At least 5 distinct types of the marker chromosome were detected and some of them were probably derived from each other (dynamic mosaicism). The proposita had an MCA pattern consistent with mild cat eye syndrome, while her sister and her mother had some of the manifestations described in this syndrome. A specific correlation could be established between phenotype and karyotype.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/10. The phenotype of a 45,X male with a Y/18 translocation.In this report, we describe a male infant with a 45,X karyotype; the entire short arm and the centromere of the y chromosome were translocated onto the short arm of chromosome 18, resulting in an unbalanced dicentric chromosome. Breakpoints were identified by in situ fluorescence hybridization (FISH) on the proximal Yq11 and 18p11.2. Both Y and 18 centromeric alphoid sequences were identified on the derived 18 chromosome. Clinical features were compatible with 18p- syndrome and no Turner stigmata were present in our propositus. Short stature was likely to be related to the deletion of 18p and/or Yq, where a gene involved in stature determination has been located proximal to a gene involved in spermatogenesis (AZF).- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/10. Interstitial deletion 2q33.3-q34 in a boy with a phenotype resembling the Seckel syndrome.A boy presented at 5 weeks with a syndrome of pre- and postnatal growth retardation, microcephaly, muscular hypotonia, and facial anomalies resembling those seen in Seckel syndrome or microcephalic primordial dwarfism I. Analysis of prometaphase chromosomes, fluorescent in situ hybridization (FISH), and molecular studies showed the presence of a de novo chromosome 2 deletion that could be defined as del(2)(q33.3q34)pat. Parental chromosomes were normal, except for the presence of a paternal supernumerary marker identified by FISH as der(15). On follow-up of the patient during the next months length development appeared normal and the diagnosis of Seckel syndrome was withdrawn. Clinical findings of previously published cases with interstitial deletion of at least 2q33.3-q34, the deletion present in the propositus, are reviewed and include pre- and postnatal growth retardation, psychomotor retardation, microcephaly, micrognathia, and abnormal/low-set ears; findings also present in the propositus. These findings resemble those described in the Seckel syndrome. Noteworthy is the finding that 2/3 of the 60 reviewed cases originally reported as having Seckel syndrome apparently belong to a heterogeneous group of low birth weight microcephalic dwarfism I yet to be clearly defined. In these patients no chromosome 2q deletion has been reported so far. Retrospective analysis could show if a subgroup of these patients carry submicroscopic deletions at 2q33.3-q34. Alternatively, molecular analysis of this region may be warranted in newly diagnosed patients with Seckel syndrome-like manifestations.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/10. Del (X)(p21.2) in a mother and two daughters with variable ovarian function.We report a family in which a woman with the mosaic karyotype 45,X/46,X,del(X)(p21.2) transmitted the deleted x chromosome to two daughters. The nature of the deletion was confirmed by fluorescent in situ hybridization (FISH). All three family members showed somatic Ullrich-turner syndrome features, but only one daughter had ovarian failure. These observations have implications for the diagnosis of Ullrich-turner syndrome and genotype/phenotype correlations of x chromosome deletions.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
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