Uniparental isodisomy 6 associated with deficiency of the fourth component of complement.

Welch, Thomas R.; Beischel, Linda; Choi, Edmund; Balakrishnan, Kamala; Bishof, Nancy A.

doi:10.1172/jci114760

Cited by 62 publications

(25 citation statements)

References 16 publications

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“…Differences in chromatin structure as well (Rabin et aL, 1987). The observation that paternal (Welch et aL, 1990) and maternal UPD 6 (van den Berg-Loonen et aL, submitted for publication) are compatible with nor mal human development supports our previous finding that the IGF2R gene is not imprinted (Kalscheuer et aL, 1993) and raises the possibility that this holds for the MAS gene, too. Expression and methylation studies should soon clarify this point and may shed more light as in the absence or presence of a trans-acting factor on the role of gene-specific and regional factors in the acting as a repressor by binding to the hypomethylated control of parent-specific expression, paternal CpG 2 region may account for the differential expression of the human and mouse IG F2R genes.…”

Section: Cpg 1 Is Completely Unmethylated On Both Parental Igf2r Allesupporting

confidence: 77%

“…Our results clearly demonstrate th a t the region comprising CpG 2 is methylated in a parent-specific manner. viously described patients with uniparental disomy (UPD), one with unipaternal disomy and the other with unimaternal disomy for chromosome 6 (Welch et al} 1990; van den Berg-Loonen et a l., submitted for publi cation).…”

Section: -------------------------------41 -------------------------mentioning

confidence: 99%

“…Fur thermore, both unim aternal and unipaternal disomy for the human IG F 2R gene does not give rise to specific symptoms (Welch et a l , 1990; van den Berg-Loonen et al, submitted for publication). Biallelic expression of hum an 1GF2R in various tissues was also shown by Ogawa et al (1993) and Xu et a l (1993).…”

Section: Cpg 1 Is Completely Unmethylated On Both Parental Igf2r Allementioning

confidence: 99%

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Maternal-Specific Methylation of the HumanIGF2RGene Is Not Accompanied by Allele-Specific Transcription

et al. 1996

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The hum an in su lin -lik e grow th factor type 2 recep tor gen e (IGF2R) is b ia llelica lly expressed in a variety o f fetal and adult tissu es. In contrast, the im printed m ouse Igf2r gen e is exp ressed exclu sively from the ma ternally in h erited chrom osom e. The m ouse gene con tains tw o CpG isla n d s th at are m ethylated in a parentspecific m anner. M éthylation o f th e CpG island in the prom oter region occu rs on th e repressed paternal gene copy. M éthylation of th e CpG island in intron 2 is specific for th e a ctiv e m aternal allele and m ay repre sen t the prim ary im print. H ere, we have analyzed the hum an IGF2R gen e to in v estig a te w hether these m otifs and th eir parent-of-origin-specific epigenetic modifi cation have b een conserved. As in th e mouse, the hu man IGF2R gen e w as found to contain two CpG is lands, one en com p assin g th e transcription start site (CpG 1) and th e oth er in th e second intron (CpG 2). CpG 2 is h yp erm eth ylated on th e m aternal IGF2R al lele. In contrast to th e situ a tio n in th e m ouse, how ever, the hum an CpG 1 is com p letely unm ethylated on both parental chrom osom es, The hum an and m ouse intronic CpG islan d s la ck sign ifican t sequence hom ol ogy* w h ich su g g ests th a t DNA conform ation plays a role in allele-Specific m éthylation.

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Section: Cpg 1 Is Completely Unmethylated On Both Parental Igf2r Allesupporting

confidence: 77%

Section: -------------------------------41 -------------------------mentioning

confidence: 99%

Section: Cpg 1 Is Completely Unmethylated On Both Parental Igf2r Allementioning

confidence: 99%

See 1 more Smart Citation

Maternal-Specific Methylation of the HumanIGF2RGene Is Not Accompanied by Allele-Specific Transcription

et al. 1996

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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%

“…A total of 5 further cases with TND and paternal UPD6 have since been reported in the literature (8)(9)(10)(11)(12), and another involved a child with diabetes who died at the age of 16 days (13). 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).…”

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confidence: 99%

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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Delayed diagnosis in patients with Prader-Willi syndrome due to maternal uniparental disomy 15

et al. 1997

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Prader-Willi syndrome (PWS) results from absence of the normally active paternally inherited genes on proximal 15q, due to del(15)(q11q13) or by maternal uniparental disomy (UPD) 15 in most cases. In addition to a higher frequency of hypopigmentation among deletion patients, minor phenotypic differences between deletion and UPD patients have recently been reported, including lower birth weight in the deletion group, shorter birth length in males with UPD, and shorter course of gavage feeding and later onset of hyperphagia in females with UPD. We previously reported that those with UPD had a less "typical" facial appearance, and they less often had skin picking, skill with puzzles, and high pain threshold. There were no children younger than 3.5 years of age in the UPD group, in contrast to several of them in the deletion group, suggesting a possible diagnostic delay in the UPD group. To assess this possibility and seek reasons for it, we reviewed the charts of 60 PWS patients with complete molecular testing. Mean age at diagnosis of patients with UPD was significantly higher than in the deletion group. Mean percentiles of birth weights and lengths of patients with UPD were significantly lower than in those with deletion. Mean duration of gestation, mean duration of gavage feeding, and mean age at onset of hyperphagia did not differ significantly between groups. Delay in the diagnosis of patients with UPD, which may influence the management and impact of the disorder, might be explained by a lower frequency of typical facial anomalies in this group.

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Uniparental isodisomy 6 associated with deficiency of the fourth component of complement.

Cited by 62 publications

References 16 publications

Maternal-Specific Methylation of the HumanIGF2RGene Is Not Accompanied by Allele-Specific Transcription

Maternal-Specific Methylation of the HumanIGF2RGene Is Not Accompanied by Allele-Specific Transcription

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

Delayed diagnosis in patients with Prader-Willi syndrome due to maternal uniparental disomy 15

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