Functional disomy for Xq26.3-qter in a boy with an unbalanced t(X;21)(q26.3;p11.2) translocation

Akiyama, Masaharu; Kawame, Hiroshi; Ohashi, Hirofumi; Tohma, Takaya; Ohta, Hiroko; Shishikura, Akihiro; Miyata, Ichiro; Usui, Nobuo; Eto, Yoshikatsu

doi:10.1002/1096-8628(2001)9999:9999<::aid-ajmg1150>3.0.co;2-c

Cited by 27 publications

(22 citation statements)

References 8 publications

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“…At birth, the association of severe hypoto- It is worth noting the location of the breakpoints in Xautosome translocations implicating Xq28. In five out of six cases, including our case 1, the Xq28 segment is translocated to regions rich in repeated sequences, the short arm of an acrocentric in two cases 9,11 and the region distal to the unique subtelomeric probe in three cases including our case 1. 13 The euchromatic part of the Y long arm that is implicated in the five cases of Xq -Yq translocation is rich in repeat units, yielding massive palindromes.…”

Section: Xq -Yq Translocationsmentioning

confidence: 64%

Functional disomy of the Xq28 chromosome region

et al. 2005

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We report on two patients, a boy and a girl, with an additional Xq28 chromosome segment translocated onto the long arm of an autosome. The karyotypes were 46,XY,der(10)t(X;10)(q28;qter) and 46,XX,der(4)t(X;4)(q28;q34), respectively. In both cases, the de novo cryptic unbalanced X-autosome translocation resulted in a Xq28 chromosome functional disomy. To our knowledge, at least 17 patients with a distal Xq chromosome functional disomy have been described in the literature. This is the third report of a girl with an unbalanced translocation yielding such a disomy. When the clinical features of both patients are compared to those observed in patients reported in the literature, a distinct phenotype emerges including severe mental retardation, facial dysmorphic features with a wide face, a small mouth and a thin pointed nose, major axial hypotonia, severe feeding problems and proneness to infections. A clinically oriented FISH study using subtelomeric probes is necessary to detect such a cryptic rearrangement.

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Section: Xq -Yq Translocationsmentioning

confidence: 64%

Functional disomy of the Xq28 chromosome region

et al. 2005

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“…41 The boy presented with pre-and postnatal growth retardation, developmental delay, hypotonia, microcephaly, agenesis of the corpus callosum, dysmorphic facial features, cryptorchism and left multidysplastic kidney, but not with situs ambiguus, cardiac malformation and sacral or anal anomalies. Since the latter anomalies have been ascribed to loss-of-function mutations of ZIC3 in man and in addition to gain-of-function mutations in Xenopus, 8 this might indicate that in this case ZIC3 in the translocated Xq segment is inactivated by the same mechanisms, as discussed above, thus excluding it from the functional disomy of the remainder of the translocated Xq segment.…”

Section: Discussionmentioning

confidence: 99%

Situs ambiguus in a female fetus with balanced (X;21) translocation – evidence for functional nullisomy of the ZIC3 gene?

et al. 2004

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The human ZIC3 gene has been mapped to Xq26.2, the visceral heterotaxy locus HTX1, and has been shown to be mutated in X-linked situs ambiguus and/or complex heart defects. We report on a female fetus with situs ambiguus, asplenia and corrected transposition of the great arteries, displaying a (X;21) translocation. The balanced state of the t(X;21)(q26;p13) was verified by FISH on metaphase chromosomes of the fetus using DOP-PCR products of the microdissected der(21) and Xq-subtelomere specific sequences, and by PRINS with b-satellite specific sequences. Examination with polymorphic markers flanking ZIC3 on DOP-PCR products of the microdissected der(21) chromosome evidenced that the complete copy of the ZIC3 gene was translocated to chromosome 21. Mutations in the fetal and parental ZIC3 genes were excluded by sequencing. Paternal origin of the der(X) and der(21) chromosomes was confirmed by use of polymorphic microsatellite markers from chromosome 21 and from the chromosomal region Xq26, respectively. X chromosome inactivation analysis using a PCR of a polymorphic (CAG) n repeat in the first exon of the androgen receptor gene showed a completely skewed X inactivation pattern with the paternal X as the active X chromosome, thus excluding functional disomy of distal Xq. A positional effect caused by the balanced (X;21) translocation may be responsible for functional nullisomy of ZIC3 and thus explain the situs and cardiac abnormalities in the fetus.

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“…Mental, psychomotor and growth retardation as well as craniofacial anomalies, hypotonia, hypoplastic genitalia, spina bifida and feeding difficulties are significant issues in individuals carrying Xq26-q27 duplications. 10,[12][13][14][15][16] Cryptorchidism is an additional clinical feature present in patients with larger duplications that affect Xq28 region (Table 1; Figure 3), which suggests that the gene responsible for this pathology might be located at the Xq28. Given the relatively small size of the duplication we present here, it could help to identify the genes responsible for the phenotype associated with distal Xq duplications.…”

Section: Discussionmentioning

confidence: 99%

“…Xq26.2-q26.3 duplication and mental retardation I Madrigal et al are patients carrying Xq27 duplications who do not present hypopituitarism, 15,37 which may be explained by hypopituitarism presenting with incomplete penetrance, or by the lack of diagnosis. Regarding spina bifida, accepting that there is a causative gene for this trait in the long arm of the X chromosome, some authors narrowed the critical region to Xq26.2 [16], which is not in agreement with our findings.…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of Xq duplications is still unknown, and only few have been reported. [6][7][8][9][10][11][12][13][14][15][16] To date, cryptic duplications encompassing MECP2 gene seem to be the most frequent microduplication syndrome responsible for cognitive impairment in patients with Xq distal duplications. Approximately 1% of unexplained XLMR may be caused by MECP2 duplications.…”

Section: Introductionmentioning

confidence: 99%

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Xq26.2-q26.3 microduplication in two brothers with intellectual disabilities: clinical and molecular characterization

et al. 2010

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Partial duplications involving the long arm of the X chromosome are associated with mental retardation, short stature, microcephaly, hypopituitarism and a wide range of physical findings. We identified an inherited Xq26.2-Xq26.3 duplication in two brothers with severe mental retardation, hypotonia, growth delay, craniofacial disproportion and dental malocclusion. Chromosome analysis was normal and multiplex ligation-dependent probe amplification analysis detected duplication on Xq26. Further characterization by array comparative genomic hybridization and quantitative PCR helped to determine proximal and distal duplication breakpoints giving a size of approximately 2.8 Mb. The duplication encompasses 24 known genes, including the X-linked mental retardation genes ARHGEF6, PHF6, HPRT1 and SLC9A6. Clinical and molecular characterization of Xq duplications will shed more light into the phenotypic implication of functional disomy of X-chromosome genes.

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Functional disomy for Xq26.3-qter in a boy with an unbalanced t(X;21)(q26.3;p11.2) translocation

Cited by 27 publications

References 8 publications

Functional disomy of the Xq28 chromosome region

Functional disomy of the Xq28 chromosome region

Situs ambiguus in a female fetus with balanced (X;21) translocation – evidence for functional nullisomy of the ZIC3 gene?

Xq26.2-q26.3 microduplication in two brothers with intellectual disabilities: clinical and molecular characterization

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