Prenatal Diagnosis and Carrier Detection for a Point Mutation in UBE3A Causing Angelman Syndrome

Tsai, Ting-Fen; Raas‐Rothschild, Annick; Ben‐Neriah, Ziva; Beaudet, Arthur L.

doi:10.1086/302120

Cited by 17 publications

(13 citation statements)

References 16 publications

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“…The type and frequency of mutations we detected are in agreement with the results reported by other groups (Fang et al 1999;Fung et al 1998;Kishino et al 1997;Malzac et al 1998;Matsuura et al 1997;Moncla et al 1999a;Tsai et al 1998). The type and frequency of mutations we detected are in agreement with the results reported by other groups (Fang et al 1999;Fung et al 1998;Kishino et al 1997;Malzac et al 1998;Matsuura et al 1997;Moncla et al 1999a;Tsai et al 1998).…”

Section: Discussionsupporting

confidence: 92%

Screening for UBE3A gene mutations in a group of Angelman syndrome patients selected according to non-stringent clinical criteria

1999

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The Angelman syndrome (AS) is caused by genetic abnormalities affecting the maternal copy of chromosome region 15q12. Until recently, the molecular diagnosis of AS relied on the detection of either a deletion at 15q11-13, a paternal uniparental disomy (UPD) for chromosome 15 or imprinting mutations. A fourth class of genetic defects underlying AS was recently described and consists of mutations of the UBE3A gene. The vast majority of mutations reported so far are predicted to cause major disruptions at the protein level. It is unclear whether mutations with less drastic consequences for the gene product could lead to milder forms of AS. We report on our results obtained by screening 101 clinically diagnosed AS patients for mutations in the UBE3A gene. Non-stringent clinical criteria were purposely applied for inclusion of AS patients in this study. The mutation search was carried out by single-strand conformation polymorphism (SSCP), and SSCP/restriction fragment length polymorphism (RFLP) analyses and revealed five novel UBE3A gene mutations as well as three different polymorphisms. All five mutations were detected in patients with typical features of AS and are predicted to cause frameshifts in four cases and the substitution of a highly conserved residue in the fifth. The results we obtained add to the as yet limited number of reports concerning UBE3A gene mutations. Important aspects that emerge from the data available to date is that the four classes of genetic defects known to underlie AS do not appear to cover all cases. The genetic defect underlying approximately 10% of AS cases, including some familial cases, remains unknown.

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Section: Discussionsupporting

confidence: 92%

Screening for UBE3A gene mutations in a group of Angelman syndrome patients selected according to non-stringent clinical criteria

1999

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“…As the only inherited multiple nucleotide deletion (case NS 27) originated post-zygotically in the mother, a mosaic carrier, this case should be excluded from the analysis, resulting in a significant association between inheritance and type of mutation (P ¼ 0.02; Fisher's exact test). In order to test this hypothesis, we reviewed all the mutations published in the literature taking into account their inheritance status and excluding mosaicism [Kishino et al, 1997;Matsuura et al, 1997;Fung et al, 1998;Malzac et al, 1998;Tsai et al, 1998;Baumer et al, 1999;Fang et al, 1999;Russo et al, 1999Russo et al, , 2000Hitchins et al, 2004;Rapakko et al, 2004;Hosoki et al, 2005;Bonaglia et al, 2007]. We found that the proportion of multiple nucleotide deletions and insertions occurring de novo (28/46 ¼ 0.61) almost doubled that of the single nucleotide substitutions (7/22 ¼ 0.32), and this difference was significant (P ¼ 0.015).…”

Section: Discussionmentioning

confidence: 95%

“…2. Distribution of missense/nonsense, in-frame and frameshift mutations in exons 8-16 of UBE3A gene described in the literature [Kishino et al, 1997;Matsuura et al, 1997;Fung et al, 1998;Malzac et al, 1998;Tsai et al, 1998;Baumer et al, 1999;Fang et al, 1999;Russo et al, 1999Russo et al, , 2000Hitchins et al, 2004;Rapakko et al, 2004;Hosoki et al, 2005;Bonaglia et al, 2007;present work].…”

Section: Discussionmentioning

confidence: 99%

Novel UBE3A mutations causing Angelman syndrome: Different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions

Camprubí

Guitart

Gabau

et al. 2009

American J of Med Genetics Pt A

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Angelman syndrome (AS) is a genetic disorder caused by a deficiency of UBE3A imprinted gene expression from the maternal chromosome 15. In 10% of AS cases the genetic cause is a mutation affecting the maternal copy of the UBE3A gene. In two large Spanish series of clinically stringently selected and nonstringently selected patients, we have identified 11 pathological mutations--eight of them novel mutations--and 14 sequence changes considered polymorphic variants. Remarkably, single nucleotide substitutions are more likely to be inherited, while multiple nucleotide deletions or insertions are less frequently inherited, thus indicating that single nucleotide substitutions are more likely to originate from the paternal germline. Additionally, there seems to be a different distribution of nucleotide changes and multiple nucleotide deletions or insertions along the UBE3A gene sequence.

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“…Frequencies ranging from 5-6 % (Malzac et al,1998;Fang et al, 1999) to 20-30% (Tsai et al,1998) are indicated by current data on normally methylated patients.…”

Section: Introductionmentioning

confidence: 79%

“…A wide genetic heterogeneity underlies the clinical phenotype (Stalker et al,1998) as: a) ∼ 70% of the patients have typical large "de novo" deletions on maternal chromosome 15q11-q13, giving a risk of recurrence (RR) < 1%, b) 1-2% have rarer structural chromosome anomalies with a variable recurrence, c) ∼ 5% have paternal UPD for chromosome 15 with a RR< 1%, d) 2-9% carry Imprinting Centre (IC) mutations (RR: 50% for female carriers) (Stalker et al1998 ;Tsai et al,1998) and e) 5-6 % have UBE3A gene (MIM# 601623) mutations (RR: 50% for female carriers) (Malzac et al,1998;Fang et al, 1999). The methylation pattern is diagnostic for the first four classes of patients who show only the paternal unmethylated allele, while the remaining class has biparental methylation patterns (Glenn et al,1993) .…”

Section: Introductionmentioning

confidence: 99%

Novel mutations of ubiquitin protein ligase 3A gene in Italian patients with Angelman syndrome

et al. 2000

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Prenatal Diagnosis and Carrier Detection for a Point Mutation in UBE3A Causing Angelman Syndrome

Cited by 17 publications

References 16 publications

Screening for UBE3A gene mutations in a group of Angelman syndrome patients selected according to non-stringent clinical criteria

Screening for UBE3A gene mutations in a group of Angelman syndrome patients selected according to non-stringent clinical criteria

Novel UBE3A mutations causing Angelman syndrome: Different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions

Novel mutations of ubiquitin protein ligase 3A gene in Italian patients with Angelman syndrome

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