Abnormal neurodevelopment outcome in case of neonatal hyperekplexia secondary to missense mutation in GLRB gene

Hyperekplexia is an exaggerated startle to external stimuli associated with a generalised increase in tone seen in neonates with both sporadic and genetic predisposition. This is an uncommon neurological entity that is misdiagnosed as seizure. A 28-days-old infant was admitted to us with characteristic intermittent generalised tonic spasm being treated as a seizure disorder. The infant had characteristic stiffening episode, exaggerated startle and non-habituation on tapping the nose. Hyperekplexia was suspected and confirmed by genetic testing (mutation in the β subunit of glycine was found). Initial improvement was seen with the use of clonazepam, which was not sustained. At the age of 4.5 years, the child is still having neurobehavioural issues like hyperactivity and sensory hyper-responsiveness. Usually, hyperekplexia is benign in nature. We report a case of hyperekplexia with non-sense mutation in the β subunit of GlyR gene having abnormal neurodevelopmental findings at 4.5 years.

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Hyperekplexia in a neonate: a seizure mimicker

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20175755 ◽

2017 ◽

Vol 6 (1) ◽

pp. 375

Author(s):

Sunil Kumar Agarwalla ◽

Debasis Patro ◽

Nasreen Ali ◽

Ankita Pattanaik

Keyword(s):

Clinical Diagnosis ◽

Genetic Predisposition ◽

Startle Reflex ◽

Seizure Disorder ◽

Disease Entity ◽

Startle Disease ◽

Tonic Spasm ◽

External Stimuli

Hyperekplexia is an exaggerated startle to external stimuli associated with generalized increase in tone seen in a normal newborn with both sporadic as well as genetic predisposition. This is an uncommon neurological entity that is often confused with seizure in infancy. To date about 150 cases have been reported in the literature. We report a 6-week-old infant with characteristic intermittent generalized tonic spasm misdiagnosed as seizure disorder and was on phenobarbitone. With characteristic stiffening episode and exaggerated startle without habituation on tapping the nose we came to a clinical diagnosis of Hyperekplexia or Stiff baby syndrome or Startle disease. The child was started on Clonazepam to which he responded remarkably with decreased startle reflex. The aim of this case reporting is to through insight to this disease entity when we see an intermittent hypertonic infant.

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Human oocyte maturation arrest caused by a novel missense mutation in TUBB8

Journal of International Medical Research ◽

10.1177/0300060518778638 ◽

2018 ◽

Vol 46 (9) ◽

pp. 3759-3764 ◽

Cited By ~ 7

Author(s):

Jingjing Xiang ◽

Wei Wang ◽

Chunfeng Qian ◽

Jiangyang Xue ◽

Ting Wang ◽

...

Keyword(s):

Genetic Testing ◽

Missense Mutation ◽

Oocyte Maturation ◽

Clinical Examination ◽

Sanger Sequencing ◽

Mutation Screening ◽

Pcr Amplification ◽

Human Oocyte ◽

Maturation Arrest ◽

Class Viii

Objective To explore the etiology of human oocyte maturation arrest in two infertile Chinese sisters. Methods Clinical examination and genetic testing of all available family members were conducted, and the findings were used to create a pedigree. Mutation screening using PCR amplification and DNA Sanger sequencing of the entire tubulin beta 8 class VIII gene ( TUBB8) including intron–exon boundaries was performed to identify mutations. Results A novel missense TUBB8 mutation (c.1054G > T, p.A352S) in the patient and her elder sister was detected and shown to be associated with oocyte maturation arrest. Conclusion Our findings expand the known mutation spectrum of TUBB8 and provide insights into the etiology of human oocyte maturation arrest.

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Current Approaches to Germline Cancer Genetic Testing

Annual Review of Medicine ◽

10.1146/annurev-med-052318-101009 ◽

2020 ◽

Vol 71 (1) ◽

pp. 85-102

Author(s):

Elena M. Stoffel ◽

John M. Carethers

Keyword(s):

Genetic Testing ◽

Clinical Education ◽

Genetic Predisposition ◽

Genomic Medicine ◽

Cancer Therapies ◽

Clinical Genetic ◽

Clinical Genetic Testing ◽

Sequencing Technologies ◽

Predisposition Genes ◽

Generation Sequencing

The prevalence of genetic predisposition to cancer is greater than initially appreciated, yet most affected individuals remain undiagnosed. Deleterious germline variants in cancer predisposition genes are implicated in 1 in 10 cases of advanced cancer. Next-generation sequencing technologies have made germline and tumor DNA sequencing more accessible and less expensive. Expanded access to clinical genetic testing will improve identification of individuals with genetic predisposition to cancer and provide opportunities to effectively reduce morbidity through precision cancer therapies and surveillance. Cross-disciplinary clinical education in genomic medicine is needed to translate advances in genomic medicine into improved health outcomes.

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A Novel Missense Mutation (C522Y) Is Present in the β-Hexosaminidase β-Subunit Gene of a Japanese Patient with Infantile Sandhoff Disease

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1995.2007 ◽

1995 ◽

Vol 212 (2) ◽

pp. 564-571 ◽

Cited By ~ 18

Author(s):

Y. Kuroki ◽

K. Itoh ◽

Y. Nadaoka ◽

T. Tanaka ◽

H. Sakuraba

Keyword(s):

Missense Mutation ◽

Japanese Patient ◽

Sandhoff Disease ◽

Β Subunit ◽

Subunit Gene

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Two novel SCN1A mutations identified in families with familial hemiplegic migraine

Cephalalgia ◽

10.1177/0333102414529195 ◽

2014 ◽

Vol 34 (13) ◽

pp. 1062-1069 ◽

Cited By ~ 23

Author(s):

Claudia M Weller ◽

Nadine Pelzer ◽

Boukje de Vries ◽

Mercè Artigas López ◽

Oriol De Fàbregues ◽

...

Keyword(s):

Genetic Testing ◽

Missense Mutation ◽

Direct Sequencing ◽

Familial Hemiplegic Migraine ◽

The Other ◽

Kinetic Properties ◽

Functional Domain ◽

Amino Acid Residues ◽

Hemiplegic Migraine ◽

Scn1a Gene

Background Familial hemiplegic migraine (FHM) is a rare monogenic subtype of migraine with aura, characterized by motor auras. The majority of FHM families have mutations in the CACNA1A and ATP1A2 genes; less than 5% of FHM families are explained by mutations in the SCN1A gene. Here we screened two Spanish FHM families for mutations in the FHM genes. Methods We assessed the clinical features of both FHM families and performed direct sequencing of all coding exons (and adjacent sequences) of the CACNA1A, ATP1A2, PRRT2 and SCN1A genes. Results FHM patients in both families had pure hemiplegic migraine with highly variable severity and frequency of attacks. We identified a novel SCN1A missense mutation p.Ile1498Met in all three tested hemiplegic migraine patients of one family. In the other family, novel SCN1A missense mutation p.Phe1661Leu was identified in six out of eight tested hemiplegic migraine patients. Both mutations affect amino acid residues that either reside in an important functional domain (in the case of Ile1498) or are known to be important for kinetic properties of the NaV1.1 channel (in the case of Phe1661). Conclusions We identified two mutations in families with FHM. SCN1A mutations are an infrequent but important cause of FHM. Genetic testing is indicated in families when no mutations are found in other FHM genes.

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A Family with Liddle’s Syndrome Caused by a New Missense Mutation in the β Subunit of the Epithelial Sodium Channel

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.6.5030 ◽

1998 ◽

Vol 83 (6) ◽

pp. 2210-2213 ◽

Cited By ~ 5

Author(s):

Junnosuke Inoue ◽

Taisuke Iwaoka ◽

Hiroshi Tokunaga ◽

Kazufumi Takamune ◽

Shojiro Naomi ◽

...

Keyword(s):

Sodium Channel ◽

Missense Mutation ◽

Sodium Current ◽

Epithelial Sodium Channel ◽

Missense Mutations ◽

Β Subunit ◽

Dominant Form ◽

Liddle’S Syndrome ◽

Liddle's Syndrome ◽

Py Motif

Liddle’s syndrome is an autosomal dominant form of salt sensitive hypertension caused by mutations in the β or γ subunit of the epithelial sodium channel. Systemic mutagenesis studies revealed that a conserved PPPXY sequence (PY motif) of the C-terminus of the α, β, or γ subunits might be involved in the regulation of the channel activity. However, only two missense mutations in the PY motif of theβ subunit have been reported to cause Liddle’s syndrome. We sequenced the C-termini of the β and γ subunits of the epithelial sodium channel in a Japanese family clinically diagnosed as having Liddle’s syndrome and found a new missense mutation in the PY motif of the β subunit, P615S. Expression studies with P615S mutant in Xenopus oocytes resulted in an about 3-fold increase in the amiloride-sensitive sodium current compared to the wild type (p = 0.001). These findings provide further clinical evidence for the hypothesis that a conserved PY motif may be critically important for the regulation of the epithelial sodium channel.

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The Right Not to Know and the Duty to Tell: The Case of Relatives

The Journal of Law Medicine & Ethics ◽

10.1111/jlme.12117 ◽

2014 ◽

Vol 42 (1) ◽

pp. 38-52 ◽

Cited By ~ 7

Author(s):

Niklas Juth

Keyword(s):

Genetic Testing ◽

Genetic Predisposition ◽

Genetic Information ◽

Preventive Measures ◽

Right To Know ◽

Potential Conflict ◽

Conflict Of Interests ◽

Right Not To Know ◽

The Right ◽

Future Plans

This text is about obtaining and sharing genetic information when there is a potential conflict of interests between patients and their families and relatives. The patient or, in this text, the “index-person,” is someone who is considering obtaining or already has obtained genetic information about herself through genetic testing.The index-person can have several reasons to take an interest in obtaining her genetic information. She may want to know if she has a genetic predisposition for a disorder in order to take measures for preventing its development. Even if there are no preventive measures, as is the case with Huntington's disease, for instance, she may still want to know whether she has the mutation, in order to adjust her future plans. These interests that an individual may have in obtaining genetic information have been used to argue in favour of a right to know.

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Non-BRCA1/2 Variants Detected in a High-Risk Chilean Cohort With a History of Breast and/or Ovarian Cancer

Journal of Global Oncology ◽

10.1200/jgo.18.00163 ◽

2019 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Christina Adaniel ◽

Francisca Salinas ◽

Juan Manuel Donaire ◽

Maria Eugenia Bravo ◽

Octavio Peralta ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

High Risk ◽

Genetic Predisposition ◽

Cancer Syndrome ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Pathogenic Variants ◽

Cancer Program ◽

Genetic Test Results

PURPOSE Little is known about the genetic predisposition to breast and ovarian cancer among the Chilean population, in particular genetic predisposition beyond BRCA1 and BRCA2 mutations. In the current study, we aim to describe the germline variants detected in individuals who were referred to a hereditary cancer program in Santiago, Chile. METHODS Data were retrospectively collected from the registry of the High-Risk Breast and Ovarian Cancer Program at Clínica Las Condes, Santiago, Chile. Data captured included index case diagnosis, ancestry, family history, and genetic test results. RESULTS Three hundred fifteen individuals underwent genetic testing during the study period. The frequency of germline pathogenic and likely pathogenic variants in a breast or ovarian cancer predisposition gene was 20.3%. Of those patients who underwent testing with a panel of both high- and moderate-penetrance genes, 10.5% were found to have pathogenic or likely pathogenic variants in non- BRCA1/2 genes. CONCLUSION Testing for non- BRCA1 and -2 mutations may be clinically relevant for individuals who are suspected to have a hereditary breast or ovarian cancer syndrome in Chile. Comprehensive genetic testing of individuals who are at high risk is necessary to further characterize the genetic susceptibility to cancer in Chile.

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