Lethal neonatal rigidity and multifocal seizure syndrome – Report of another family with a BRAT1 mutation

Straussberg, Rachel; Ganelin‐Cohen, Esther; Goldberg-Stern, Hadassah; Tzur, Shay; Behar, Doron M.; Smirin‐Yosef, Pola; Salmon‐Divon, Mali; Basel‐Vanagaite, Lina

doi:10.1016/j.ejpn.2014.11.004

Cited by 31 publications

(43 citation statements)

References 8 publications

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“…For the patient described in this report, on serial neuroimaging she had similar findings of cerebellar hypoplasia, thin corpus callosum, and focal encephalomalacia, all suggestive of neuronal loss. However, because her neurological picture is less severe compared to some patients with BRAT1-related disease who have had normal neuroimaging [Puffenberger et al, 2012;Saunders et al, 2012;Straussberg et al, 2015], other factors may contribute more to the marked encephalopathy observed. Mitochondrial dysfunction could be a factor, but evidence against this in our patient includes lack of an elevated lactate peak on brain MRS, and no respiratory chain complex deficiencies in muscle.…”

Section: Discussionmentioning

confidence: 82%

“…The patients characterized to date have all exhibited a phenotype of neonatal onset hypertonia, intractable seizures, frequent apneic episodes, microcephaly and stagnant head growth, and lack of any developmental progress [Puffenberger et al, 2012;Saunders et al, 2012;Saitsu et al, 2014;Straussberg et al, 2015]. All died before 6 months of age, with the exception of one patient who survived 21 months.…”

Section: Introductionmentioning

confidence: 94%

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BRAT1‐related disease—identification of a patient without early lethality

Mundy

Krock

Mao

et al. 2015

American J of Med Genetics Pt A

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We present a patient with neonatal onset of hypertonia and seizures identified through whole exome sequencing to have compound heterozygous variants, c.294dupA (p.Leu99fs) and c.1925C>A (p.Ala642Glu), in the BRCA1-associated protein required for ATM activation-1 (BRAT1) gene. Variants in BRAT1 have been identified to cause lethal neonatal rigidity and multifocal seizure syndrome (OMIM# 614498), which consistently manifests a severe neurological phenotype that includes neonatal presentation of rigidity and hypertonia, microcephaly and arrested head growth, intractable seizures, absence of developmental progress, apneic episodes, and death usually by 6 months of age. Our patient initially had a similarly severe neurological picture but remains alive at 6 years of age, expanding the phenotype to include longer term survival and providing further insights into genotype-phenotype correlations and the natural history of this disease.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 94%

BRAT1‐related disease—identification of a patient without early lethality

Mundy

Krock

Mao

et al. 2015

American J of Med Genetics Pt A

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“…9 One new report described two siblings born to consanguineous Arab-Muslim parents who have mutations in the same gene, with myoclonic seizures, progressive microcephaly, hypertonia, and apnea-bradycardia. 11 Our case also had microcephaly and hypertonia; however, he was still alive at the age of 4.5 years and no seizures were observed by parents, therapists or clinicians; no paroxysmal events were recorded during the sleep and sleep-deprived video-EEG either.…”

Section: Discussionmentioning

confidence: 63%

“…8–11 The seven earlier described cases suffered from refractory epilepsy, and all of them died in their first months of life. We describe a new patient with compound heterozygous BRAT1 mutations and PE but with some atypical characteristics; he is alive at the age of 4.5 years and he never presented seizures.…”

Section: Introductionmentioning

confidence: 99%

Mutations in BRAT1 cause autosomal recessive progressive encephalopathy: Report of a Spanish patient

Fernández-Jaén

Álvarez²,

et al. 2016

European Journal of Paediatric Neurology

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We describe a 4-year-old male child born to non-consanguineous Spanish parents with progressive encephalopathy (PE), microcephaly, and hypertonia. Whole exome sequencing revealed compound heterozygous BRAT1 mutations [c.1564G > A (p.Glu522Lys) and c.638dup (p.Val214Glyfs*189)]. Homozygous and compound heterozygous BRAT1 mutations have been described in patients with lethal neonatal rigidity and multifocal seizure syndrome (MIM# 614498). The seven previously described patients suffered from uncontrolled seizures, and all of those patients died in their first months of life. BRAT1 acts as a regulator of cellular proliferation and migration and is required for mitochondrial function. The loss of these functions may explain the cerebral atrophy observed in this case of PE. This case highlights the extraordinary potential of next generation technologies for the diagnosis of rare genetic diseases, including PE. Making a prompt diagnosis of PE is important for genetic counseling and disease management.

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“…Neonates with such gene mutations have hypertension, persistent seizures, frequent episodes of apnea, microcephaly, stagnation in the development of the head, lack of any development progress [10,11] and most patients survived until 21 months. DNA sequencing analysis data identified heterozygous variations in BRCA1 gene.…”

Section: The Involvement Of Brca1 Gene In Patients With Premature Mormentioning

confidence: 99%

The Role of BRCA1 and BRCA2 Genes in the Appearance of Pediatric and Adolescent Disorders

Drikos¹,

Sachinidis²,

Vassi³

et al. 2017

J Neoplasm

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The genes BRCA1 and BRCA2 appear crucial role in development of hereditary breast and ovarian cancer. Hundreds of different types of mutations have been identified in these genes. The high risk mutations inactivate a very important and foolproof DNA repair process, thus increasing considerably the risk of diseases development such as breast and ovarian cancer.These genes seem to have a significant influence and participation in appearance of pediatric diseases other than breast and ovarian cancer being important molecules in DNA repair process and cell cycle progression. Therefore further exploration and evaluation of these genes in the appearance of pediatric diseases may enhance the importance of prenatal audit.

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Lethal neonatal rigidity and multifocal seizure syndrome – Report of another family with a BRAT1 mutation

Cited by 31 publications

References 8 publications

BRAT1‐related disease—identification of a patient without early lethality

BRAT1‐related disease—identification of a patient without early lethality

Mutations in BRAT1 cause autosomal recessive progressive encephalopathy: Report of a Spanish patient

The Role of BRCA1 and BRCA2 Genes in the Appearance of Pediatric and Adolescent Disorders

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