First patient with trisomy 21 accompanied by an additional der(4)(:p11 → q11:) plus partial uniparental disomy 4p15‐16

Starke, Heike; Mitulla, Beate; Nietzel, Angela; Heller, Anita; Beensen, Volkmar; Grosswendt, Gisela; Claussen, Uwe; Eggeling, Ferdinand von; Liehr, Thomas

doi:10.1002/ajmg.a.10830

Cited by 15 publications

(14 citation statements)

References 14 publications

(15 reference statements)

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“…A partial UPD 4p was detected in case 10 (for details, see Starke et al 2003), and complete maternal UPD 22 plus partial paternal UPD 11 was determined in case 29 (Fig. 5c).…”

Section: Smc-related Chromosomal Mosaicsmentioning

confidence: 93%

“…BAC or YAC DNA (200 ng) was amplified by degenerate oligonucleotideprimed PCR (DOP-PCR; 50-µl volume; Senger et al 1998). Each probe was labeled separately by using a secondary DOP-PCR (20-µl volume) either with SpectrumGreen or TexasRed as described in Nietzel et al (2001) Case also reported in Starke et al (2003) e Case also reported in Starke et al (2001) f Case also reported in Nietzel et al (2002) beling schemes shown in Fig. 1a.…”

Section: Subcenm-fish Methodsmentioning

confidence: 99%

“…Furthermore, the exact origin of the SMC can be subsequently determined by cenM-FISH or CM-FISH (Henegariu et al 2001). Both approaches enable the one-step identification of all human centromeric regions and have been successfully used for the characterization of SMCs von Eggeling et al 2002;Liehr et al 2002aLiehr et al , 2002bStarke et al 2003). If routine cytogenetics reveals that the SMC belongs in class 1, acroM-FISH (Langer et al 2001) or acrocenM-FISH (Trifonov et al 2003) can be alternatively applied.…”

Section: Smc Classificationmentioning

confidence: 99%

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Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification

Starke¹,

Nietzel²,

Weise³

et al. 2003

Hum Genet

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154

151

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Small supernumerary marker chromosomes (SMCs) are present in about 0.05% of the human population. In approximately 30% of SMC carriers (excluding the approximately 60% SMC derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. The clinical outcome of an SMC is difficult to predict as they can have different phenotypic consequences because of (1). differences in euchromatic DNA-content, (2). different degrees of mosaicism, and/or (3). uniparental disomy (UPD) of the chromosomes homologous to the SMC. Here, we present 35 SMCs, which are derived from all human chromosomes, apart from chromosome 6, as demonstrated by the appropriate molecular cytogenetic approaches, such as centromere-specific multicolor fluoresence in situ hybridization (cenM-FISH), multicolor banding (MCB), and subcentromere-specific multicolor FISH (subcenM-FISH). In nine cases without an aberrant phenotype, neither partial proximal trisomies nor UPD could be detected. Abnormal clinical findings, such as psychomotoric retardation and/or craniofacial dysmorphisms, were associated with seven of the cases in which subcentromeric single-copy probes were proven to be present in three copies. Conversely, in eight cases with a normal phenotype, proximal euchromatic material was detected as partial trisomy. UPD was studied in 12 cases and subsequently detected in two of the cases with SMC (partial UPD 4p and maternal UPD 22 in a der(22)-syndrome patient), indicating that SMC carriers have an enhanced risk for UPD. At present, small proximal trisomies of 1p, 1q, 2p, 6p, 6q, 7q, 9p, and 12q seem to lead to clinical manifestations, whereas partial proximal trisomies of 2q, 3p, 3q, 5q, 7p, 8p, 17p, and 18p may not be associated with significant clinical symptoms. With respect to clinical outcome, a classification of SMCs is proposed that considers molecular genetic and molecular cytogenetic characteristics as demonstrated by presently available methods.

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“…A partial UPD 4p was detected in case 10 (for details, see Starke et al 2003), and complete maternal UPD 22 plus partial paternal UPD 11 was determined in case 29 (Fig. 5c).…”

Section: Smc-related Chromosomal Mosaicsmentioning

confidence: 93%

Section: Subcenm-fish Methodsmentioning

confidence: 99%

Section: Smc Classificationmentioning

confidence: 99%

See 1 more Smart Citation

Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification

Starke¹,

Nietzel²,

Weise³

et al. 2003

Hum Genet

Self Cite

154

151

View full text Add to dashboard Cite

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“…In only three of these the origin of the sSMC was identified. Two were derived from chromosome 15, and one from chromosome 4 (Heppell-Parton and Waters, 1991; Starke et al, 2003a, cases 10 and 23). The other 22 reports were published in the pre-FISH era and thus are not informative for this review.…”

Section: Inv Dup(15) Cases and Ssmc Not Correlated With Known Clinicamentioning

confidence: 99%

Small supernumerary marker chromosomes (sSMC) in humans

Liehr¹,

Claussen²,

Starke³

2004

Cytogenet Genome Res

258

277

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Small supernumerary marker chromosomes (sSMC), defined as additional centric chromosome fragments too small to be identified or characterized unambiguously by banding cytogenetics alone, are present in 0.043% of newborn children. Several attempts have been made to correlate certain sSMC with a specific clinical picture, resulting in the description of several syndromes such as the i(18p)-, der(22)-, i(12p)- (Pallister Killian syndrome) and inv dup(22)- (cat-eye) syndromes. However, most of the remaining sSMC including minute-, ring-, inverted-duplication- as well as complex-rearranged chromosomes, have not yet been correlated with clinical syndromes, mostly due to problems in their comprehensive characterization. Here we present an overview of sSMC, including the first attempt to address problems of nomenclature and their modes of formation, problems connected with mosaicism plus familial occurrence. The review also discusses the frequency of sSMC in prenatal, postnatal, and clinical cases, their chromosomal origin and their association with uniparental disomy. A short review of the up-to-date approaches available for sSMC characterization is included. Clinically relevant correlations concerning the presence of a specific sSMC and its phenotypic consequences should become available soon.

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“…Only five cases of maternal UPD for chromosome 4 have been reported so far. Three were partial UPDs, involving 4q21 -35 in a Japanese man affected by abetalipoproteinaemia, 15 4p13 -16 in a patient affected by Ellis-van Creveld syndrome, 16 and 4p15 -16 in a child with trisomy 21; 17 one was a complete UPD in a normally developed foetus who died in the uterus probably because of the high level of mosaicism for trisomy 4 found in placental trophoblast, 18 and one was a case of isochromosome 4 (46, À4, À4, þ i4q, þ i4p) in a woman with multiple miscarriages. 19 This study describes the first case of congenital afibrinogenaemia caused by uniparental isodisomy (iUPD) of chromosome 4 containing a novel homozygous large deletion (approximately 15 kb).…”

Section: Introductionmentioning

confidence: 99%

Congenital afibrinogenaemia caused by uniparental isodisomy of chromosome 4 containing a novel 15-kb deletion involving fibrinogen Aα-chain gene

et al. 2004

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Among rare inherited deficiencies of coagulation factors, congenital afibrinogenaemia is characterised by the lack of fibrinogen in plasma. In the last few years, several genetic defects underlying afibrinogenaemia (mostly point mutations) have been described in the fibrinogen gene cluster. In this study, the molecular basis responsible for afibrinogenaemia in a Thai proband was defined. Point mutation screening was accomplished by directly sequencing the three fibrinogen genes. The impossibility to amplify fibrinogen Aa-chain gene (FGA) exons 5 and 6 suggested the presence of a homozygous deletion. A specific longrange PCR assay enabled the identification of a novel 15-kb deletion, representing the largest afibrinogenaemia-causing deletion described so far. Direct sequencing of the deletion junction allowed mapping of the breakpoints in FGA intron 4 and in the intergenic region between Aa-and Bb-chain genes. Since the mutation was inherited only from the mother and nonpaternity was ruled out, a maternal uniparental disomy (UPD) was hypothesised. UPD test, carried out with markers covering the whole chromosome 4, revealed that maternal isodisomy was responsible for homozygosity of the 15-kb deletion in the proband. The apparently normal phenotype of the proband, except for afibrinogenaemia, suggests that UPD for chromosome 4 is clinically silent. This represents the first case of a documented complete isodisomy of chromosome 4 causing the phenotypic expression of a recessive disorder. In silico analyses of the regions surrounding the breakpoints suggested that the 15-kb deletion might have originated from an inappropriate repair of a double-strand break by the nonhomologous end joining mechanism.

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First patient with trisomy 21 accompanied by an additional der(4)(:p11 → q11:) plus partial uniparental disomy 4p15‐16

Cited by 15 publications

References 14 publications

Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification

Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification

Small supernumerary marker chromosomes (sSMC) in humans

Congenital afibrinogenaemia caused by uniparental isodisomy of chromosome 4 containing a novel 15-kb deletion involving fibrinogen Aα-chain gene

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