Unbalanced segregation of a complex four-break 5q23-31 insertion in the 5p13 band in a malformed child.
ABSTRACT A rec(5)dup(5)(q23.2q31.3) inherited from a maternal ins(5)(p13.1q23.2q31.3) was detected in a 4-month-old male child who showed hypotonia, microcephaly, cardiac defects, pulmonary hypoplasia and stenosis, bilateral hydronephrosis, hydrocele, testicular hypoplasia and phimosis. Dysmorphisms were also observed. We compare the clinical characteristics of our patient with those of the previously reported dup5q cases in an attempt to define the phenotype-karyotype correlation. The maternal insertion responsible for the duplicated 5q23.2-31.3 region in the child was characterized in detail by FISH analysis, which identified a complex rearrangement involving four breakpoints (bkp's): a 5q segment excised following breakage at 5q23.2 and 5q31.3 became inverted and inserted at 5p13.1, probably coincidentally with an internal breakage at 5q23.3 causing a 180 degrees rotation of the two subsegments. The mother's karyotype was consequently defined as 46,XX, ins(5)(pter --> p13.1 Colon, two colons q23.3 --> q23.2 Colon, two colons q31.3 --> q23.3 Colon, two colons p13.1 --> q23.2 Colon, two colons q31.3 --> qter). There are clusters of Alu sequences in the genomic clones spanning all the four bkp's, suggesting their possible involvement in the rearrangement. No clinical phenotype was associated with this balanced rearrangement in the mother and a number of other carriers in the same family.
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ABSTRACT: We report a child with multiple malformations caused by trisomy for the distal part of the long arm of chromosome No 5. A neonatal diagnosis of Down's syndrome had previously been made on the basis of clinical examination and the detection of an additional chromosome not unlike No 21. A subsequent clinical re-evaluation, with the cooperation of the parents who permitted further studies, led to the confirmation of the true diagnosis. The mother was the carrier of a balanced translocation between chromosome No 5 and No 14. The child had severe growth and psychomotor retardation and characteristic features: microcephaly, antimongoloid slant, epicanthus, low set ears, down-turned mouth, and long upper lip. She was hypertonic and a congenital heart disease (atrial septal defect) was present. We have compared this case with others known to be trisomic for segment 5q31-qter.Archives of Disease in Childhood 05/1988; 63(4):427-31. · 3.05 Impact Factor
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ABSTRACT: We report on an infant with an as yet undescribed partial duplication 5q(q22----5q33). He had a number of the already recorded manifestations of partial trisomy 5q, namely microcephaly, growth retardation, brachydactyly, long flat philtrum, thin upper lip vermilion and downturned angles of mouth and apparently low set ears. He survived only 6 months. He inherited his duplication from a maternal intrachromosomal insertion; thus he represents a pure dup(5)(q22----5q33).American Journal of Medical Genetics 02/1985; 20(1):57-62.
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ABSTRACT: Emery-Dreifuss muscular dystrophy (EMD) is an X-linked disorder characterized by contractures, progressive muscle weakness and cardiomyopathy. The emerin gene, located in human Xq28, is approximately 2 kb in length, is composed of 6 exons and falls within a 219-kb region that has been completely sequenced. Immediately centromeric to emerin is the 26-kb filamin gene (FLN1), composed of 48 exons and encoding the actin-binding protein 280 (refs 7,8). Flanking this 48-kb FLN1/emerin region are two large inverted repeats, each 11.3 kb, that exhibit > 99% sequence identity. The high level of genomic detail in this region allowed us to characterize the first complete emerin gene deletion mutation that also involved a partial duplication of the nearby FLN1 gene. This rearrangement could be explained by mispairing of the large inverted repeats, followed by double recombination among one set of mispaired repeats and internal sequences. Furthermore, our characterization of this rare DNA rearrangement revealed a more common result of the mispairing of these large inverted repeats--recombination contained within the inverted repeats leading to the maintenance of repeat sequence homogeneity and inversion of the 48-kb FLN1/emerin region. The presence of this frequent inversion, found in the heterozygous state in 33% of females, helps to explain the discrepancies observed between the genetic and physical map distances in this region of the X chromosome. It also illustrates the biological insights which can be gleaned by sequencing the human genome.Nature Genetics 05/1997; 16(1):96-9. · 35.21 Impact Factor