Recessive hyperekplexia due to a new mutation (R100H) in the <i>GLRA1</i> gene

Coto, Eliécer; Armenta, D; Espinosa, Raúl; Argente, Jesús; Castro, Marisa; Álvarez, Victoria

doi:10.1002/mds.20637

Cited by 17 publications

(6 citation statements)

References 12 publications

(19 reference statements)

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“…[1][2][3][4] Most known genetic mutations resulting in hyperekplexia involve the GLRA1 gene of the inhibitory glycine receptor. 2,[6][7][8][9][10] The inhibitory glycine receptor mediates synaptic inhibition, primarily in the brain stem and spinal cord. [11][12] That the affected members in family K6456 were found to be heterozygous for the arginine271proline mutation in GLRA1 while the unaffected members of the family were negative for the mutation strongly supports our assertion that hyperekplexia in this family is likely because of the arginine271proline mutation.…”

Section: Discussionmentioning

confidence: 99%

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A Novel GLRA1 Mutation Associated with An Atypical Hyperekplexia Phenotype

et al. 2008

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Hyperekplexia (MIM #149400) is a rare neurological disorder characterized by an exaggerated startle response, infantile hypertonia and hyperreflexia without spasticity, a hesitant gait that usually improves by 3 years of age, and nocturnal myoclonus. Familial hyperekplexia is usually autosomal dominant resulting from mutations in the inhibitory glycine receptor subunit alpha 1 (GLRA1) gene on chromosome 5q. We identified a 3-generation family with progressively severe phenotypes of hyperekplexia. All affected family members were found to be heterozygous for a novel arginine271proline mutation in GLRA1. Long-term follow-up of the affected members of the third generation, now aged 6 and 7 years, reveals enhanced startle responses and persistent hypertonia of the extremities without clonus or a catch, tight heel cords and abnormal toe-walking gait, and plantar flexor reflexes. The 7-year-old child recently reponded well to a benzodiazepine. Future studies are warranted to examine whether this new missense mutation is solely responsible for this atypical phenotype.

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Section: Discussionmentioning

confidence: 99%

“…5 The majority of these genetic mutations are alterations of the inhibitory glycine receptor alpha 1 subunit (GLRA1), located on chromosome 5q. 2,[6][7][8][9][10] This results in disruption of inhibitory synaptic responses.…”

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confidence: 99%

A Novel GLRA1 Mutation Associated with An Atypical Hyperekplexia Phenotype

et al. 2008

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“…In 1993, mutations were identified in the main hyperekplexia gene, GLRA1, located on chromosome 5q33‐q35 4, 5. A point mutation in the α subunit of the glycine receptor gene GLRA1 has been identified in most pedigrees with the “major” form hyperekplexia,4, 6–10 and may be regarded the defining element of autosomal dominant ‘major’ hyperekplexia. In a few families homozygous mutations10 or compound heterozygosity8, 9 in the GLRA1 gene have been reported.…”

Section: Discussionmentioning

confidence: 99%

A novel GLRA1 mutation in a recessive hyperekplexia pedigree

et al. 2007

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“…At least one non-penetrant GLRA1 mutation has been reported. 48 There are also rare cases of hyperekplexia caused by homozygosity [49][50][51][52] or compound heterozygosity 52,53 for recessive GLRA1 mutations.…”

Section: Geneticsmentioning

confidence: 99%

“…One double-blind, placebo controlled, cross-over study that included four patients revealed that patients on clonazepam had reduced startle activity compared to vigabatrin as measured by startle to auditory stimuli. 67 Despite often dramatic response to clonazepam, 2,4,[7][8][9]16,23,25,26,29,30,[49][50][51]53,67 there are other reports that have found clonazepam to be less effective. 5,11,16,27,31,61 Saenz-Lope et al 27 found clonazepam ineffective in their three patients but had some success with the use of valproic acid and a combination of hydroxytryptophan and piracetam.…”

Section: Clonazepammentioning

confidence: 99%

Hyperekplexia: Treatment of a Severe Phenotype and Review of the Literature

Mineyko

Whiting

Graham

2011

Can. J. Neurol. Sci.

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Hyperekplexia is a syndrome of exaggerated startle response to tactile, auditory, or other stimuli. 1 Patients can present early in the neonatal period with episodes of stiffening that can be so severe as to cause apnea and death, 2-9 a phenotype often referred to as "stiff-baby syndrome." 5 With time, the life-threatening manifestations of hyperekplexia are replaced by startle responses that are characterized by stiffening and falls. 2,5,8,10 Less severely affected patients experience excessive startle without significant stiffening. 11 Onset of symptoms can occur after the neonatal period and can be into adulthood. 12,13 Hyperekplexia is understood to be a monogenic, though heterogeneous, disorder. Autosomal dominant, autosomal recessive, and apparently sporadic forms (that are more likely the result of de novo mutations) have been recognized. 14 Mutations responsible for hyperekplexia have been found in the alpha 1 subunit of the glycine receptor gene (GLRA1), 15 the beta glycine receptor subunit gene (GLRB), 16 the presynaptic sodiumand chloride-dependent glycine transporter 2 gene ABSTRACT: Hyperekplexia is a rare disorder caused by autosomal dominant or recessive modes of inheritance and characterized by episodes of exaggerated startle. Five causative genes have been identified to date. The syndrome has been recognized for decades and due to its rarity, the literature contains mostly descriptive reports, many early studies lacking molecular genetic diagnoses. A spectrum of clinical severity exists. Severe cases can lead to neonatal cardiac arrest and death during an episode, an outcome prevented by early diagnosis and clinical vigilance. Large treatment studies are not feasible, so therapeutic measures continue to be empiric. A marked response to clonazepam is often reported but refractory cases exist. Herein we report the clinical course and treatment response of a severely affected infant homozygous for an SLC6A5 nonsense mutation and review the literature summarizing the history and genetic understanding of the disease as well as the described comorbidities and treatment options. RÉSUMÉ: Hyperekplexie : traitement d'un phénotype sévère et revue de la littérature. L'hyperekplexie est une maladie caractérisés par des épisodes de réaction exagérée de sursaut et dont le mode d'hérédité peut être dominant ou récessif. À ce jour, cinq gènes différents ont été identifiés. Le syndrome est connu depuis plusieurs dizaines d'années et, à cause de sa rareté, la littérature fait état surtout de descriptions de cas dont plusieurs, surtout les premières, ne comportent pas de diagnostic moléculaire. La sévérité clinique est très variable et, chez les cas sévères, la maladie peut entraîner un arrêt cardiaque dans la période néonatale et le décès, ce qui peut être prévenu par un diagnostic précoce et une surveillance clinique. Son traitement demeure empirique parce qu'il n'est pas possible d'effectuer de grandes études sur ce sujet. Bien qu'une excellente réponse au clonazépam soit souvent rapportée, il existe des cas ré...

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Recessive hyperekplexia due to a new mutation (R100H) in the GLRA1 gene

Cited by 17 publications

References 12 publications

A Novel GLRA1 Mutation Associated with An Atypical Hyperekplexia Phenotype

A Novel GLRA1 Mutation Associated with An Atypical Hyperekplexia Phenotype

A novel GLRA1 mutation in a recessive hyperekplexia pedigree

Hyperekplexia: Treatment of a Severe Phenotype and Review of the Literature

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