1/6. Uniparental isodisomy resulting from 46,XX,i(1p),i(1q) in a woman with short stature, ptosis, micro/retrognathia, myopathy, deafness, and sterility.We report on a 43-year-old woman who was referred for evaluation because of minor facial anomalies, myopathy, sterility, short stature, hearing loss, downward slant of palpebral fissures, bilateral ptosis, severe micro/retrognathia, high arched palate, and scoliosis. Cytogenetic analyses utilizing GTG/CBG bandings showed presence of one i(1p) and one i(1q) without normal chromosome 1 homologues. fluorescence in situ hybridization analysis showed hybridization to only two chromosomes, consistent with the G-banded interpretation of i(1p) and i(1q). To the best of our knowledge, this is the first case of isochromosomes 1p and 1q replacing the two normal chromosome 1s. Molecular investigations using markers for chromosome 1 showed inheritance of only one set of paternal alleles and absence of any maternal alleles in the patient. The adverse phenotype of the patient may be due to one or more recessive mutations, genomic imprinting, or a combination of both.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/6. Molecular cytogenetic evaluation in a patient with a translocation (3;21) associated with blepharophimosis, ptosis, epicanthus inversus syndrome (BPES).blepharophimosis, ptosis, epicanthus inversus syndrome type I (BPES; OMIM 110100) is an autosomal dominant disorder affecting craniofacial development and ovarian function. We have identified a patient with BPES who carried a de novo reciprocal translocation [46, XX,t(3;21)(q23;q22.1)]. fluorescence in situ hybridization analysis at band 3q23 using probes derived from BAC 175G20 (research Genetics), PACs 108L15 and 169C10 (RPCI1), and cosmids AC174D4, AC68D3, AC44F5, and AC125C5 (Lawrence Livermore National Laboratory) was performed. The patient's breakpoint was found to lie within the overlapping region of the BAC and PACs but centromeric to all the cosmids. However, a 10.5-kb BamHI-digested fragment, common to the BAC and PAC clones, was shown to cross the breakpoint. The results have placed our patient's breakpoint proximal to that of the previously reported patient [46,XY,t(3;4)(q23;p15.2)] and within a 10.5-kb interval. This is the second patient in which a breakpoint was refined by molecular cytogenetics. Our findings emphasize the significance of this region for BPES.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
3/6. PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation.Congenital aniridia is due to deletions and point mutations in the PAX6 gene. We describe here a case of a mother and her two sons with a syndrome comprising congenital aniridia, ptosis, and slight mental retardation. The sons also show behavioral changes. The possibility of deletion around the PAX6 locus was excluded by polymorphism studies and fluorescence in situ hybridization analysis. mutation screening of the PAX6 gene revealed the presence of a transversion C719A, resulting in the substitution of arginine for serine at residue 119. We suggest that this missense mutation is responsible both for aniridia and ptosis, and possibly also for the observed cognitive dysfunction in this family.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
4/6. Pure direct duplication (12)(q24.1-->q24.2) in a child with Marcus Gunn phenomenon and multiple congenital anomalies.Partial trisomy of the region 12q24.1-->q24.2 is rare and usually associated with other rearrangements. We report on the clinical and cytogenetic findings in a girl with a pure de novo direct duplication dup(12)(q24.1-->q24.2). She had developmental and growth retardation, facial dysmorphism with upslanting palpebral fissures, wide downturned mouth, short neck, and Marcus Gunn phenomenon. She also had single transverse creases, hypoplasia of the corpus callosum, and cardiac malformations consisting of a bicuspid aortic valve, multiple ventricular septal defects, and kinking of the aorta. The size of the duplication was characterized by molecular cytogenetics and comparative genomic hybridization (CGH) to be 11.5 Mb in size and extended from the BAC probe RP11-256L11 loci (108.2 Mb) /- 1 Mb to the BAC probe RP11-665J20 loci (119.7 Mb) /- 1 Mb. No such pure 12q24 duplication was detected out of the 23 patients reported in the literature with duplications in 12q region. Comparison with these reported 12q trisomies suggests the duplication dup(12)(q24.1-->q24.2) is associated with a recognizable phenotype consisting of characteristic facial dysmorphism, growth retardation, and cardiac malformation.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
5/6. WAGR(O?) syndrome and congenital ptosis caused by an unbalanced t(11;15)(p13;p11.2)dn demonstrating a 7 megabase deletion by FISH.aniridia usually occurs in isolation, but may also occur as part of the WAGR contiguous gene deletion syndrome, which includes wilms tumor, aniridia, genitourinary abnormalities, and mental retardation. The aniridia and predisposition for wilms tumor seen in WAGR are caused by haploinsufficiency for PAX 6 and WT1, respectively. We present a female infant with aniridia, bilateral ptosis, bilateral posterior capsular cataracts, nystagmus, left-sided glaucoma, microcephaly, mild unilateral hydronephrosis, poor linear growth, and gross motor delay consistent with a clinical diagnosis of wagr syndrome. In addition, weight-for-height ratio at 12 months is at the 94th centile, raising the possibility of a diagnosis of WAGRO (WAGR obesity). Chromosome analysis revealed a translocation (11;15)(p13;p11.2) which has not been previously associated with a diagnosis of WAGR. Subsequent clinical WAGR fluorescent in situ hybridization (FISH) analysis demonstrated a deletion of 11p13 including PAX6 and WT1. A complete FISH-mapping of the breakpoints on chromosome 11 revealed a 7 Mb deletion within 11p13-11p14. The patient is examined in light of other reported patients with deletions and/or translocations involving the regions between 11p12 --> 11p14 including patients with WAGR obesity (WAGRO) as well as with other reported patients with aniridia and congenital ptosis.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
6/6. Familial occurrence of neuroblastoma, von Recklinghausen's neurofibromatosis, Hirschsprung's agangliosis and jaw-winking syndrome.A family is reported with ganglioneuromas in the mother and neuroblastomas in her two daughters co-existing with cases of von Recklinghausen's neurofibromatosis, Hirschsprung's agangliosis, and the jaw-winking syndrome in other family members. There were no detectable constitutional chromosomal defects in the family even when high resolution techniques were applied. Similarly, dna-hybridization analysis did not reveal gross molecular rearrangements in the vicinity of the proto-oncogenes N-myc-, c-myc, neu, and N-ras. However, the aggregation of several rare, autosomal dominant diseases affecting tissue derived from the neural crest not only suggest a link between te pathogenesis of these disease, but also makes it highly likely that a single mutation segregating within the family is responsible for this association.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |