Gly802Asp Substitution in the
proα2(l) Collagen Chain in a Family
with Recurrent Osteogenesis
imperfecta due to Paternal
Mosaicism

Lund, Allan Meldgaard; Schwartz, Marianne; Raghunath, Michael; Steinmann, Beat; Skovby, Flemming

doi:10.1159/000472168

Cited by 34 publications

(36 citation statements)

References 25 publications

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“…It has been estimated that 10% to 20% of ostensibly de novo cases of retinoblastoma, 9 hemophilia B, 10 Duchenne muscular dystrophy, 8 and hemophilia A 20 are the result of parental mosaicism for these genetic disorders. Examples of germ-line mosaicism in asymptomatic parents have been documented in several autosomal dominant genetic diseases, including neurofibromatosis, 21 osteogenesis imperfecta, 22 and hypertrophic cardiomyopathy. 23 The R1623Q mutation was first reported in an Asian female infant who, like our proband, presented perinatally with 2:1 AV block, lengthened QT interval, cardiac failure, and life-threatening ventricular arrhythmias.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Third-Trimester Fetal Loss and Maternal Mosaicism for Long-QT Syndrome

et al. 2004

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Background-The importance of germ-line mosaicism in genetic disease is probably underestimated, even though recent studies indicate that it may be involved in 10% to 20% of apparently de novo cases of several dominantly inherited genetic diseases. Methods and Results-We describe here a case of repeated germ-line transmission of a severe form of long-QT syndrome (LQTS) from an asymptomatic mother with mosaicism for a mutation in the cardiac sodium channel, SCN5A. A male infant was diagnosed with ventricular arrhythmias and cardiac decompensation in utero at 28 weeks and with LQTS after birth, ultimately requiring cardiac transplantation for control of ventricular tachycardia. The mother had no ECG abnormalities, but her only previous pregnancy had ended in stillbirth with evidence of cardiac decompensation at 7 months' gestation. A third pregnancy also ended in stillbirth at 7 months, again with nonimmune fetal hydrops. The surviving infant was found to have a heterozygous mutation in SCN5A (R1623Q), previously reported as a de novo mutation causing neonatal ventricular arrhythmia and LQTS. Initial studies of the mother detected no genetic abnormality, but a sensitive restriction enzyme-based assay identified a small (8% to 10%) percentage of cells harboring the mutation in her blood, skin, and buccal mucosa. Cord blood from the third fetus also harbored the mutant allele, suggesting that all 3 cases of late-term fetal distress resulted from germ-line transfer of the LQTS-associated mutation. Conclusions-Recurrent late-term fetal loss or sudden infant death can result from unsuspected parental mosaicism for LQTS-associated mutations, with important implications for genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Recurrent Third-Trimester Fetal Loss and Maternal Mosaicism for Long-QT Syndrome

et al. 2004

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“…Protein-chemical methods included sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of (pro)collagen I, cyanogen bromide peptides (for protein-mapping) and trypsin-treated collagen I (for determination of denaturation temperature) (Lund et al, 1996). Molecular studies.…”

Section: Methodsmentioning

confidence: 99%

“…To quantify mutant alleles, PCR was done with one primer of a primer-pair labelled with [ 32 P]ATP. The PCR products were cleaved with relevant restriction enzymes, and after electrophoresis the autoradiogram was scanned and the proportion of the mutant to normal allele calculated (Lund et al, 1996).…”

Section: Methodsmentioning

confidence: 99%

Osteogenesis imperfecta: Mosaicism and refinement of the genotype-phenotype map in OI type III

et al. 1999

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“…Radiolabelled procollagen I was obtained from cell cultures incubated at 30°C and 37°C in medium containing 2,3,-[ (Lund et al, 1996a;Steinmann et al, 1984). Procollagen I was processed and analysed by SDS-polyacrylamide gel electrophoresis (Lund et al, 1996;Steinmann et al, 1984;Laemmli, 1970).…”

Section: Protein-chemical Studiesmentioning

confidence: 99%

“…All PCR reactions were done in a Cetus Thermal Cycler and carried out as described by Lund et al (1996a). For amplification of cDNA sequences the primers 9A and 14B (biotinylated) and for genomic DNA sequences the primers 4A and 17B were used (Table 1).…”

Section: Amplification Of Cdna/genomic Dna Sequences and Sequence Anamentioning

confidence: 99%

(G586V) substitutions in the α1 and α2 chains of collagen I: Effect of α-chain stoichiometry on the phenotype of osteogenesis imperfecta?

Lund¹,

Skovby²,

Schwartz³

1997

Hum. Mutat.

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Gly802Asp Substitution in the proα2(l) Collagen Chain in a Family with Recurrent Osteogenesis imperfecta due to Paternal Mosaicism

Cited by 34 publications

References 25 publications

Recurrent Third-Trimester Fetal Loss and Maternal Mosaicism for Long-QT Syndrome

Recurrent Third-Trimester Fetal Loss and Maternal Mosaicism for Long-QT Syndrome

Osteogenesis imperfecta: Mosaicism and refinement of the genotype-phenotype map in OI type III

(G586V) substitutions in the α1 and α2 chains of collagen I: Effect of α-chain stoichiometry on the phenotype of osteogenesis imperfecta?

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