Paternal isodisomy for chromosome 2 as the cause of Crigler–Najjar type I syndrome

Petit, François; Gajdos, Vincent; Parisot, Frédéric; Capel, Liliane; Aboura, Azzedine; Lachaux, Alain; Tachdjian, Gérard; Poüs, Christian; Labrune, Philippe

doi:10.1038/sj.ejhg.5201342

Cited by 38 publications

(27 citation statements)

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“…Apart from the AR disorders, two of these patients appeared phenotypically normal in all other aspects. The third case presented with psychomotor delay (was not able to sit alone at 11 months) and the child passed away at 1 year of age (Petit et al, 2005). The patient in the current study presented with postnatal short stature, severe intellectual disability, dysmorphism, and heart malformations.…”

Section: Discussionmentioning

confidence: 72%

“…Paternal isodisomy of chromosome 2 has only been reported previously in three cases (Chavez et al, 2000;Thompson et al, 2002;Petit et al, 2005). All three cases were identified as having different autosomal recessive (AR) disorders: 5-alpha-reductase deficiency (Chavez et al, 2000), retinal dystrophy (Thompson et al, 2002) and Crigler-Najjar syndrome (Petit et al, 2005), resulting from reduction to homoallelism of a disease-causing mutation of paternal origin. Apart from the AR disorders, two of these patients appeared phenotypically normal in all other aspects.…”

Section: Discussionmentioning

confidence: 92%

“…Due to low number of reported UPD cases, i.e. paternal isodisomy for chromosome 2 and 7 (Chavez et al, 2000;Thompson et al, 2002;Petit et al, 2005;Le Caignec et al, 2007), a much broader phenotype might exist than what is known today due to deregulation of imprinted genes and/or mosaicism (Neiswanger et al, 2006). Alternatively, unidentified autosomal recessive traits located on the paternal chromosome 2 could be responsible for the patient's abnormal phenotype.…”

Section: Discussionmentioning

confidence: 99%

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A 1q44 deletion, paternal UPD of chromosome 2 and a deletion due to a complex translocation detected in children with abnormal phenotypes using new SNP array technology

Talseth‐Palmer

Meldrum

Nicholl

et al. 2009

Cytogenet Genome Res

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Children with intellectual disability, dysmorphic features, malformations and/or growth abnormalities frequently display normal karyotypes. Recent studies have shown that genome-wide single nucleotide polymorphism (SNP) arrays can be effective in detecting abnormalities involving copy number variation (CNV), deletions, duplications and loss of heterozygosity (LOH) that routine cytogenetic tests fail to identify. Five patients with various degrees of intellectual disability and/or dysmorphic features and other malformations were whole-genome genotyped using the Human-1 Genotyping BeadChip – Exon-Centrix 100K SNP arrays (Illumina). All patients had undergone routine cytogenetic testing; four patients had normal karyotypes, while one patient had an apparently balanced complex translocation involving chromosomes 1q25, 1q32, 2q23, 7q22 and 16q24. We detected deletions on chromosome 1q44 and 13q31.1 in one patient, and LOH of the entire chromosome 2 in another patient, both with cytogenetically normal karyotypes. The patient with the complex translocation had a deletion on chromosome 7q22.2-22.3, which is in conjunction with one of the translocation breakpoints. Our findings provide further evidence of there being a critical region for the development of microcephaly and corpus callosum abnormalities in children with distal 1q deletions. We have also shown that apparently balanced complex translocations might not be balanced at the DNA level, and we report the fourth case of paternal uniparental disomy of chromosome 2. The results of this study suggest that it may be desirable to investigate idiopathic mental retardation using genome-wide SNP arrays, in conjunction with other cytogenetic and molecular techniques.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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A 1q44 deletion, paternal UPD of chromosome 2 and a deletion due to a complex translocation detected in children with abnormal phenotypes using new SNP array technology

Talseth‐Palmer

Meldrum

Nicholl

et al. 2009

Cytogenet Genome Res

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“…2 We also discussed this deletion in one of our previous publication. 3 Wild-type UGT1A1 contains two consecutive phenylalanine in position 170 and 171. Modification of this hydrophobic region of UGT1A1 (these two phenylalanine are located in a membrane-embedded helix) may be responsible for a modification of the enzymatic activity.…”

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confidence: 99%

“…This deletion could be referred to 508_510delTTC, 509_511delTCT, 510_512delCTT, 511_513delTTC, 512_514delTCT or 513_515delCTT because it is undistinguishable at the molecular level. 3 Since the recommendations established by Antonarakis and the Nomenclature Working Group in 1998, 5 the most 3' is arbitrarily assigned to describe small deletions in repetitive sequences. In consequence, the deletion described as p.Phe170del by Ritter et al in 1993 is the same one as this described by D'Apolito et al…”

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confidence: 99%

Comments on Seven novel mutations of the UGT1A1 gene in patients with unconjugated hyperbilirubinemia by D'Apolito et al.

Petit¹,

Hébert²,

Gajdos³

et al. 2007

Haematologica

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1 The authors analysed UGT1A1 gene in 11 unrelated patients with neonatal hyperbilirubinemia. They described seven novel mutations responsible for Crigler-Najjar syndrome type I or II. However, this paper raises several questions that we wish to address.Some of these mutations are not novel and have been previously reported. Indeed, the c.513_515delCTT deletion, identified in patients 1 and 2, has been initially reported by Ritter et al in 1993. 2 We also discussed this deletion in one of our previous publication.3 Wild-type UGT1A1 contains two consecutive phenylalanine in position 170 and 171. Modification of this hydrophobic region of UGT1A1 (these two phenylalanine are located in a membrane-embedded helix) may be responsible for a modification of the enzymatic activity. 4 In this repetitive genomic sequence, it is impossible to determine exactly which nucleotides are deleted. This deletion could be referred to 508_510delTTC, 509_511delTCT, 510_512delCTT, 511_513delTTC, 512_514delTCT or 513_515delCTT because it is undistinguishable at the molecular level.3 Since the recommendations established by Antonarakis and the Nomenclature Working Group in 1998, 5 the most 3' is arbitrarily assigned to describe small deletions in repetitive sequences. In consequence, the deletion described as p.Phe170del by Ritter et al. in 1993 is the same one as this described by D'Apolito et al.The c.652_653insT insertion (responsible for the modification of the protein sequence p.Ser218PhefsX40), identified at the heterozygous state in patient 4 has already been described in our laboratory in 2004.5 At the date of this publication, we only found this insertion at the heterozygous state in association with the heterozygote A(TA)7TAA polymorphism in the TATAbox in a Polish Crigler Najjar type I patient. Currently, the second allelic mutation was identified in this patient and surprisingly was the same as that observed by D'Apolito et al. in their patient 4. The observation of two rare heterozygote genetic variations in two different families affected by a rare genetic disease, originating from two different countries is a very exceptional genetic situation. It would be interesting to confront our observations and to collaborate on this specific point.There is confusion in the nucleotide numbering of the first mutation described in this paper. 1 In the UGT1A1 cDNA referring sequence (Genebank accession number NM_000463), nucleotides in positions 717 and 718 are not AG but GA. This genetic region presents a quadruple AG-repetition. As indicated previously, genetic modifications in repetitive sequence have to be arbitrarily assigned on the 3' side. 5 Thus, this deletion has to be located at position 722_723 referring to the UGT1A1 cDNA sequence. The peptide sequence is not modified until the glutamic acid in position 241 which is replaced by a glycine. The deletion introduces a stop codon at position 16 (p.Glu241GlyfsX16).There is an error in the description of the predicted protein consequence of the last reported mutation. 1 The deletio...

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Disorders of Bilirubin Metabolism

Chowdhury

2009

The Liver

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Paternal isodisomy for chromosome 2 as the cause of Crigler–Najjar type I syndrome

Cited by 38 publications

References 25 publications

A 1q44 deletion, paternal UPD of chromosome 2 and a deletion due to a complex translocation detected in children with abnormal phenotypes using new SNP array technology

A 1q44 deletion, paternal UPD of chromosome 2 and a deletion due to a complex translocation detected in children with abnormal phenotypes using new SNP array technology

Comments on Seven novel mutations of the UGT1A1 gene in patients with unconjugated hyperbilirubinemia by D'Apolito et al.

Disorders of Bilirubin Metabolism

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