Human Gene Mutation Database (HGMD<sup>®</sup>): 2003 update

Stenson, Peter D.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew David; Shiel, Jacqueline A.; Thomas, Nicholas Stuart Tudor; Abeysinghe, Shaun S.; Krawczak, Michael; Cooper, David Neil

doi:10.1002/humu.10212

Cited by 1,692 publications

(1,515 citation statements)

References 18 publications

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“…The mutation for sample 39 has been reported before [Tang et al, 2006]. Of possible significance, 10 of the 20 non-sense mutations were associated with the codon for Arginine (CGA→TGA) compared with 20/109 non-sense mutations identified in the HGMD database [Stenson et al, 2003]. None of the changes observed in the patient samples were detected in 150 population control subjects.…”

Section: Resultsmentioning

confidence: 95%

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Identification of forty-five novel and twenty-three knownNF1 mutations in Chinese patients with neurofibromatosis type 1

Lee

You

et al. 2006

Hum. Mutat.

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Neurofibromatosis type 1 (NF1), characterized by skin neurofibromas and an excess of café-au-lait spots, is due to mutations in the neurofibromin (NF1) gene. Identifying the genetic defect in individuals with the disease represents a significant challenge because the gene is extremely large with a high incidence of sporadic mutations across the entire gene ranging from single nucleotide substitutes to large deletions. In the present study, we have used a combination of techniques (heteroduplex analysis, sequencing, loss of heterozygosity and quantification of gene dosage) to define the genetic defect in 68 individuals from a cohort of 107 NF1 Taiwanese patients of Chinese origin. Fifty-eight were initially identified using heteroduplex analytical techniques and confirmed by sequence analysis. A further five were identified by direct sequence analysis alone. The reminders were shown to carry large deletions in the NF1 gene by demonstrating loss of heterozygosity that was confirmed by gene dosage measurements using quantitative-PCR techniques. Mis-sense, non-sense, frameshift or splice-site mutations were identified across the entire gene of which the majority (45/68) were novel in nature. The detection rate with the various analytical techniques and the types of mutation detected are consistent with published data involving both individuals and large cohort studies from other ethnic backgrounds. INTRODUCTIONWith a frequency of 1/3000 live births, Neurofibromatosis type 1 (NF1; MIM# 162200) is one of the most common autosomal dominant disorders involving the human nervous system [Friedman, 1999]. The clinical features of the disease include: café-au-lait spots, cutaneous or subcutaneous neurofibromas, large plexiform neurofibromas, Lisch nodules and skin freckling. Other features such as scoliosis, macrocephaly, pseudoarthrosis, short stature, mental sub-normality and malignancies are present in a minority of patients 1997]. Except for the discoloration of the skin (Café-au-lait macules), which can be identified at a very young age, most of the other clinical features usually occur insidiously after puberty.The NF1 gene (NM_000267.1), which spans approximately 350Kb of genomic sequence on chromosome 17q11.2, is composed of 60 exons coding an 8.9Kb mRNA [Cawthon et al., 1990a;Wallace et al., 1990]. NF1 gene product, neurofibromin, is a 250 KDa hydrophilic protein comprising 2818 amino acids [Cawthon et al., 1990b]. The central region of neurofibromin displays marked homology with Ras-GTPase activation proteins (GAPs) that are involved in the negative regulation of RAS-mediated signal transduction pathways [Cichowski and Jacks, 2001].The mutation rate at the NF1 gene is estimated to be ~1x10 -4 /gamete/generation making it one of the highest of any human disease genes [Huson et al., 1989;Upadhyaya and Cooper, 1998]. Mutations encompass both single nucleotide substitutions and large genomic deletions [Stenson et al., 2003]. Approximately a half of all mutations arise de novo and do not appear to be clustered within...

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Section: Resultsmentioning

confidence: 95%

“…Mutations encompass both single nucleotide substitutions and large genomic deletions [Stenson et al, 2003]. Approximately a half of all mutations arise de novo and do not appear to be clustered within the gene.…”

Section: Introductionmentioning

confidence: 99%

Identification of forty-five novel and twenty-three knownNF1 mutations in Chinese patients with neurofibromatosis type 1

Lee

You

et al. 2006

Hum. Mutat.

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“…We considered all 37 424 non-synonymous-coding variants annotated as disease-causing in the Human Genome Mutation Database that do not overlap with known dbSNP132 positions. 53 For each of these mutations, we evaluated the sequence coverage of corresponding targets from 51 exomes, with a median coverage of 49-fold, that were sequenced in-house using the Agilent 50Mb exome kit (Agilent Technologies, Inc., Santa Clara, CA, USA) with SOLiD4 sequencing.…”

Section: Success Ratementioning

confidence: 99%

Disease gene identification strategies for exome sequencing

et al. 2012

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“…The classification of the mutations was performed according to Richards et al (2015) (Stenson et al, 2003).…”

Section: Participants and Proceduresmentioning

confidence: 99%

Is Symptomatic Long QT Syndrome Associated with Depression in Women and Men?

Wesołowska

Elovainio

Koponen

et al. 2016

Journal of Genetic Counseling

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We examined whether long QT syndrome (LQTS) mutation carrier status or symptomatic LQTS are associated with depression, and whether there are sex differences in these potential relationships.The sample comprised 782 participants (252 men). Of the 369 genetically defined LQTS mutation carriers, 169 were symptomatic and 200 were asymptomatic. The control group consisted of 413 unaffected relatives. Depression was assessed using the Beck Depression Inventory-II (BDI-II). No association was found for LQTS mutation carrier status with depression. The multinomial logistic regression showed that LQTS mutation carrier men with arrhythmic events scored higher on depression compared with the control group, even when adjusting for age, β-blockers, antidepressants, and social support (OR = 1.09, 95% CI [1.02, 1.15], p = .007). The binary logistic regression comparing symptomatic and asymptomatic LQTS mutation carriers showed that symptomatic LQTS was associated with depression in men (OR = 1.10, 95% CI [1.03, 1.19], p = .009). The results were unchanged when additionally adjusted for education. These findings suggest that symptomatic LQTS is associated with depression in men but not in women. Overall, however, depression is more frequent in women than men. Thus, regular screening for depression in LQTS mutation carriers and their unaffected family members can be important.

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Human Gene Mutation Database (HGMD^®): 2003 update

Cited by 1,692 publications

References 18 publications

Identification of forty-five novel and twenty-three knownNF1 mutations in Chinese patients with neurofibromatosis type 1

Identification of forty-five novel and twenty-three knownNF1 mutations in Chinese patients with neurofibromatosis type 1

Disease gene identification strategies for exome sequencing

Is Symptomatic Long QT Syndrome Associated with Depression in Women and Men?

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Human Gene Mutation Database (HGMD®): 2003 update

Cited by 1,692 publications

References 18 publications

Identification of forty-five novel and twenty-three knownNF1 mutations in Chinese patients with neurofibromatosis type 1

Identification of forty-five novel and twenty-three knownNF1 mutations in Chinese patients with neurofibromatosis type 1

Disease gene identification strategies for exome sequencing

Is Symptomatic Long QT Syndrome Associated with Depression in Women and Men?

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Human Gene Mutation Database (HGMD^®): 2003 update