Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23

Temple, I. Karen; Gardner, R J; Robinson, David; Kibirige, M S; Ferguson, Amy; Baum, J D; Barber, John; James, Rowena S.; Shield, Julian P H

doi:10.1093/hmg/5.8.1117

Cited by 141 publications

(84 citation statements)

References 19 publications

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“…In group 2, 11 patients were identified with a duplication of part of chromosome 6q. 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].…”

Section: Resultsmentioning

confidence: 99%

“…The association is now firmly established, although 2 cases of paternal UPD6 have been reported in older patients with no early history of TND, which cannot yet be explained (14,15). We and others have subsequently shown that several nondisomic children with TND have paternally inherited duplications within the long arm of chromosome 6 (6q23-24) (12,(16)(17)(18). Evidence from one of these families suggested that inheritance of an identical duplication from the mother did not lead to TND (16).…”

mentioning

confidence: 94%

“…We and others have subsequently shown that several nondisomic children with TND have paternally inherited duplications within the long arm of chromosome 6 (6q23-24) (12,(16)(17)(18). Evidence from one of these families suggested that inheritance of an identical duplication from the mother did not lead to TND (16). 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).…”

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confidence: 97%

“…These observations have led to the hypothesis that overexpression of a paternally expressed allele at 6q24 causes TND with no expression of the maternally inherited allele (16,21). A critical region of duplication has been mapped by Gardner et al (21) and lies within a 400-kb region of 6q24.…”

mentioning

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%

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confidence: 94%

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confidence: 97%

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confidence: 99%

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

et al. 2000

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“…These findings suggested the presence of an imprinted gene on chromosome 6. Later studies provided further evidence of the involvement of an imprinted gene in this disease and proposed that a candidate gene for TNDM lies within the chromosomal region 6q24.1-q24.3 between markers D6S1699 and D6S1010 (Temple et al, 1996;Gardner et al, 1999). Analysis of the CpG islands in the TNDM critical region for the presence of methylation differences between maternal and paternal alleles, using DNA from TNDM patients with paternal UPD 6 and normal controls, suggested LOT1/ZAC1 as a candidate imprinted gene for this disease (Gardner et al, 2000).…”

Section: Imprinting and Chromosomal Duplicationmentioning

confidence: 99%

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Abdollahi

2006

Journal Cellular Physiology

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Lost-on-transformation 1 (LOT1) (PLAGL1/ZAC1) is a member of the novel subfamily of zinc-finger transcription factors, designated as PLAG family. The other members in this group include PLAG1 and PLAGL2, which share high homology with each other and with LOT1, particularly in their zinc-finger amino-terminal region. They are structurally similar but functionally different. For example, the LOT1 gene encodes a growth suppressor protein and is localized on human chromosome 6q24-25, a chromosomal region that is frequently deleted in many types of human cancers. The gene is maternally imprinted and is linked to developmental disorders such as growth retardation and transient neonatal diabetes mellitus (TNDM). LOT1 is a target of growth factor signaling pathway(s) and silenced by epigenetic mechanisms, as well as by the loss of heterozygosity in different tumor tissues. PLAG1 is a protooncogene that is localized on chromosome 8q12 and was found to be a target of several types of chromosomal rearrangement including the one identified in pleomorphic adenomas of the salivary gland. Since the discovery of the PLAG family members in 1997, much has been learned about their structure and function, as are summarized in this review. While the available data suggest that these proteins may play important roles in regulating normal physiological functions in the mammals, a great deal more about their signaling pathway(s), potential role in the complex pathologies such as cancer and developmental disorders, and functional relationship between different family members and splice variants still remains to be uncovered.

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

1998

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We report on a 5-year-old girl with a de novo interstitial duplication of chromosome 6q21-q23 and delayed development and speech with distinctive minor facial anomalies including a "carp" mouth. Fluorescence in situ hybridization using a chromosome 6 paint probe confirms that the extra material is of chromosome 6 origin. This further delineates the dup(6q) syndrome and the manifestations due to the specific duplicated chromosomal region involved.

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Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23

Cited by 141 publications

References 19 publications

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

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

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

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

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