Partial trisomy of chromosome 6q: An interstitial duplication of the long arm

Zneimer, Susan Mahler; Ziel, Barbara; Bachman, Ronald

doi:10.1002/(sici)1096-8628(19981102)80:2<133::aid-ajmg8>3.3.co;2-2

Cited by 6 publications

(10 citation statements)

References 4 publications

(5 reference statements)

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“…These included all 7 familial cases (families K and L) and 4 sporadic cases ( (16,17), and 9 were identified using quantitative PCR of ESTs and STSs from the region (Fig. 1, ID [12][13][14][15][16][17][18][19][20]. Determining the parental origin in 9 of the duplication cases (visible and submicroscopic) was possible by testing both parents using the same method as that used for the probands.…”

Section: Resultsmentioning

confidence: 99%

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Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

et al. 2000

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Transient neonatal diabetes (TND) is a rare type of diabetes that presents soon after birth, resolves by 18 months, and predisposes to diabetes later in life. A total of 30 patients were ascertained and investigated for aberrations of chromosome 6. A genotype/phenotype study was also performed. Genotypically, these patients can be classified into 4 etiologic groups. Group 1 had paternal uniparental isodisomy of chromosome 6 (11 cases, including 1 set of identical twins). Group 2 had a duplication involving chromosome band 6q24, which was paternal in origin where tested (4 sporadic cases and 7 familial cases from 2 families). Group 3 consisted of 1 patient with a loss of methylation at a CpG island within the TND critical region (1 sporadic case). Group 4 had no identifiable rearrangement of chromosome 6 (7 sporadic cases). Most patients were growth retarded at birth, presented at a median age of 3 days, and recovered at a median age of 12 weeks. In group 2, 2 relatives of the TND patients who presented with type 2 diabetes and no early history of TND had inherited an identical duplication. An abnormality of chromosome 6 was identified in approximately 70% of sporadic TND cases and in all familial cases. No significant clinical differences were found between the 4 etiological groups. The study has broadened the clinical spectrum of TND to include type 2 diabetes presenting in later life with no neonatal presentation. The findings are consistent with an imprinted gene for diabetes mapping to 6q24, which we predict will have an important function in normal pancreatic development.

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Section: Resultsmentioning

confidence: 99%

“…This was in keeping with the 18 cases of maternal dupli-cation of the region, which have been described in the literature as without neonatal diabetes (18), and likewise TND has not been reported in maternal UPD6 (19). One additional case of duplication of 6q and TND has been reported for which the origin of the duplication is unknown (20).…”

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confidence: 99%

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

et al. 2000

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“…Several cases of TNDM were reported to be due to paternal uniparental disomy of chromosome 6 (11)(12)(13) or partial trisomy of chromosome 6q with duplication of the paternal genome (14 -17). Duplications (15) and interstitial deletions (18) of the same region of the maternally inherited chromosome 6 are not associated with the disease. These findings strongly suggest that TNDM results from the overexpression of a paternally expressed, maternally imprinted gene on chromosome 6q.…”

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confidence: 99%

Characterization of the Methylation-sensitive Promoter of the Imprinted ZAC Gene Supports Its Role in Transient Neonatal Diabetes Mellitus

Varrault

Bilanges

Mackay

et al. 2001

Journal of Biological Chemistry

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ZAC is a recently isolated zinc finger protein that induces apoptosis and cell cycle arrest. The corresponding gene is imprinted maternally through an unknown mechanism and maps to 6q24 -q25, within the minimal interval harboring the gene responsible for transient neonatal diabetes mellitus (TNDM) and a tumor suppressor gene involved in breast cancer. Because of its functional properties, imprinting status, and expression pattern in mammary cell lines and tumors, ZAC is the best candidate so far for both disease conditions. In the present work, we delineated ZAC genomic organization and mapped its transcriptional start site. It is noteworthy that the ZAC promoter localized to the CpG island harboring the methylation imprint associated with TNDM and methylation of this promoter silenced its activity. These data indicate that the methylation mark may have a direct effect on the silencing of the ZAC imprinted allele. Our findings further strengthen the hypothesis that ZAC is the gene responsible for TNDM and suggest a novel mechanism for ZAC inactivation in breast tumors.

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“…Interstitial 6q duplications are more unusual events and very few studies have reported duplications encompassing the 6q16 and/or 6q21 regions. Among them, five patients from three families have shown tandem 6q duplications [Pratt el al., 1998; Zneimer et al, ; Pazooki et al, ] and six patients from three other families have shown 6q insertional translocations in other chromosomes [Pierpont et al, ; Roland et al, ; Spreiz et al, ]. As far as we know, this is the first report of a pure interstitial 6q15q21 duplication and the second report of a familial maternal 6q duplication.…”

Section: Introductionmentioning

confidence: 62%

“…Apart from ancient SDs and well‐known recurrent microduplications such as the dup(22)(q11.2), new familial interstitial duplications have been reported in several studies[Voullaire et al, ; Mathijssen et al, ; Eussen et al, ; Kowalczyk et al, ; Leach et al, ; Mrasek et al, ; Kang et al, ] and sometimes associated with a normal phenotype [Kowalczyk et al, ; Mrasek et al, ; Kang et al, ]. With regard to 6q duplications, 13 patients have been reported with duplications encompassing the 6q16 and/or 6q21 regions [Chen et al, ; Pierpont et al, ; Roland et al, ; Pratt et al, ; Zneimer et al, ; Pazooki et al, ; Spreiz et al, ], but only one involving the 6q15q21 cytogenetic band [Spreiz et al, ] (Supplementary Table I). Most of these patients have been reported as displaying intellectual disability (11/13), postnatal growth retardation (9/13) and obesity (7/11).…”

Section: Discussionmentioning

confidence: 99%

A pure familial 6q15q21 split duplication associated with obesity and transmitted with partial reduction

Landais

Leroy

Kleinfinger³

et al. 2015

American J of Med Genetics Pt A

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Familial transmission of chromosome 6 duplications is rare. We report on the first observation of a maternally-inherited pure segmental 6q duplication split into two segments, 6q15q16.3 and 6q16.3q21, and associated with obesity. Obesity has previously been correlated to chromosome 6 q-arm deletion but has not yet been assessed in duplications. The aim of this study was to characterize the structure of these intrachromosomal insertional translocations by classic cytogenetic banding, array-CGH, FISH, M-banding and genotyping using microsatellites and SNP array analysis, in a mother and four offspring. The duplicated 6q segments, 9.75 Mb (dup 1) and 7.05 Mb (dup 2) in size in the mother, were inserted distally into two distinct chromosome 6q regions. They were transmitted to four offspring. A son and a daughter inherited the two unbalanced insertions and displayed, like the mother, an abnormal phenotype with facial dysmorphism, intellectual disability, and morbid obesity. Curiously, two daughters with a normal phenotype inherited only the smaller segment, 6q16.3q21. The abnormal phenotype was associated with the larger proximal 6q15q16.3 duplication. We hypothesize a mechanism for this exceptional phenomenon of recurrent reduction and transmission of the duplication during meiosis in a family. We expect the interpretation of our findings to be useful for genetic counseling and for understanding the mechanisms underlying these large segmental 6q duplications and their evolution.

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Partial trisomy of chromosome 6q: An interstitial duplication of the long arm

Cited by 6 publications

References 4 publications

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

Characterization of the Methylation-sensitive Promoter of the Imprinted ZAC Gene Supports Its Role in Transient Neonatal Diabetes Mellitus

A pure familial 6q15q21 split duplication associated with obesity and transmitted with partial reduction

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