Using next‐generation sequencing for the diagnosis of rare disorders: a family with retinitis pigmentosa and skeletal abnormalities

Schrader, Kasmintan A.; Heravi-Moussavi, Alireza; Waters, Paula J.; Senz, Janine; Whelan, James; Ha, Gavin; Eydoux, Patrice; Nielsen, Torsten O.; Gallagher, Barry; Boyd, Niki; Fernandez, Bridget A.; Young, Terry‐Lynn; Jones, Steven J.M.; Hirst, Martin; Shah, Sohrab P.; Marra, Marco A.; Green, Jane; Huntsman, David G.

doi:10.1002/path.2941

Cited by 32 publications

(17 citation statements)

References 24 publications

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“…In addition to these issues, we are on the threshold of a further expansion of services due to the rapid development of genetic testing technologies. For example, the use of comparative genomic hybridisation arrays as a diagnostic tool in cases of dysmorphism with developmental delay (Lee et al 2007), the introduction of non-invasive prenatal diagnosis for both single-gene disorders (Lo et al 2010) and aneuploidy (Ehrich et al 2011) and the development of next-generation sequencing for clinical use (Schrader et al 2011) will all increase the workload on genetic specialists. It is also likely that health professionals trained as genetic specialists will be required to be involved in guidance and education of other health professionals as well as delivery of direct patient care.…”

Section: Introductionmentioning

confidence: 98%

A profile of the genetic counsellor and genetic nurse profession in European countries

et al. 2011

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Quality genetic healthcare services should be available throughout Europe. However, due to enhanced diagnostic and genetic testing options, the pressure on genetic counselling services has increased. It has been shown in many countries that appropriately trained genetic counsellors and genetic nurses can offer clinical care for patients seeking information or testing for a wide range of genetic conditions. The European Society of Human Genetics is setting up a system of accreditation for genetic counsellors, to ensure safe practice, however there has been little information about the practice and education of non-medical genetic counsellors in Europe. To collect baseline data, we approached key informants (leaders in national genetics organisations or experienced practitioners) to complete an online survey, reporting on the situation in their own country. Twenty-nine practitioners responded, providing data from 18 countries. The findings indicate huge variation in genetic counsellor numbers, roles, and education across Europe. For example, in UK and The Netherlands, there are more than four counsellors per million population, while in Germany, Hungary, Turkey, and Czech Republic, there are no non-medical counsellors. There are specific educational programmes for genetic counsellors in seven countries, but only France has a specific governing legal framework for genetic counsellors. In the post-genomic era, with added pressure on health systems due to increases in availability and use of genetic testing, these disparities are likely to result in inequalities in service provided to European citizens. This study underpins the need for a coherent European approach to accreditation of genetic counsellors.

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Section: Introductionmentioning

confidence: 98%

A profile of the genetic counsellor and genetic nurse profession in European countries

et al. 2011

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“…Schrader et al [4] were the first to demonstrate the effectiveness of molecular diagnosis for ML III using NGS. They were able to show a 6-bp deletion in the GNPTG gene in a family with retinitis pigmentosa and skeletal abnormalities, patients who were not previously known to have ML III.…”

Section: Introductionmentioning

confidence: 99%

Exome sequencing for mucolipidosis III: Detection of a novel GNPTAB gene mutation in a patient with a very mild phenotype

Sperb‐Ludwig

Alegra

Velho

et al. 2015

Molecular Genetics and Metabolism Reports

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Mucolipidosis II and III alpha/beta (ML II/III alpha/beta) are rare autosomal recessive lysosomal storage diseases that are caused by a deficiency of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, the enzyme responsible for the synthesis of the mannose 6-phosphate targeting signal on lysosomal hydrolases. A Brazilian patient suspected of having a very mild ML III was investigated using whole next-generation sequencing (NGS). Two mutations in the GNPTAB gene were detected and confirmed to be in trans status by parental analysis: c.1208T>C (p.Ile403Thr), previously reported as being pathogenic, and the novel mutation c.1723G>A (p.Gly575Arg). This study demonstrates the effectiveness of using whole NGS for the molecular diagnosis of very mild ML III alpha/beta patients.

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“…ML III gamma (OMIM #252605) is caused by mutations in the gene encoding the γ-subunit of GlcNAc-1-phosphotransferase [1], [2], and is thought to be the mildest form of the disease. Very few cases of ML III gamma are reported in the literature, maybe because the disease is underdiagnosed due to its relatively mild and unspecific clinical findings, which is suggested by a recent report of ML III gamma patients diagnosed through next generation sequencing [3]. To date, approximately 28 mutations have been reported in the GNPTG gene.…”

Section: Introductionmentioning

confidence: 99%

A de novo or germline mutation in a family with Mucolipidosis III gamma: Implications for molecular diagnosis and genetic counseling

Velho

Alegra

Sperb

et al. 2014

Molecular Genetics and Metabolism Reports

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Mucolipidosis III (ML III) gamma is a very rare autosomal-recessive disorder characterized by the abnormal trafficking and subcellular localization of lysosomal enzymes due to mutations in the GNPTG gene. The present study consists of a report of a Brazilian compound heterozygote patient with ML III gamma resulting from one mutant paternal allele and one allele that had most likely undergone a de novo or maternal germline mutation. This is the first report of a de novo mutation in ML III gamma. This finding has significant implications for genetic counseling.

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Using next‐generation sequencing for the diagnosis of rare disorders: a family with retinitis pigmentosa and skeletal abnormalities

Cited by 32 publications

References 24 publications

A profile of the genetic counsellor and genetic nurse profession in European countries

A profile of the genetic counsellor and genetic nurse profession in European countries

Exome sequencing for mucolipidosis III: Detection of a novel GNPTAB gene mutation in a patient with a very mild phenotype

A de novo or germline mutation in a family with Mucolipidosis III gamma: Implications for molecular diagnosis and genetic counseling

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