scholarly journals Functional consequences of a KCNT1 variant associated with status dystonicus and early‐onset infantile encephalopathy

2019 ◽  
Vol 6 (9) ◽  
pp. 1606-1615 ◽  
Author(s):  
Tracy S. Gertler ◽  
Christopher H. Thompson ◽  
Carlos G. Vanoye ◽  
John J. Millichap ◽  
Alfred L. George
Keyword(s):  
Early Onset ◽  
Status Dystonicus ◽  
Functional Consequences

Functional consequences of genetic variation in sodium channel modifiers in early onset lone atrial fibrillation

2018 ◽  
Vol 15 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Federico Denti ◽  
Christian Paludan-Müller ◽  
Søren-Peter Olesen ◽  
Stig Haunsø ◽  
Jesper Hastrup Svendsen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Variation ◽  
Sodium Channel ◽  
Early Onset ◽  
Lone Atrial Fibrillation ◽  
Functional Consequences

scholarly journals P.070 Autosomal dominant MARS mutation linked to severe early onset CMT2U

2018 ◽  
Vol 45 (s2) ◽  
pp. S34-S35
Author(s):  
HJ McMillan ◽  
MK Gillespie ◽  
KD Kernohan ◽  
R Myer-Schuman ◽  
A Antonellis ◽  
...  
Keyword(s):  
Early Onset ◽  
Muscular Atrophy ◽  
Trna Synthetase ◽  
Cellular Growth ◽  
First Year ◽  
Wild Type ◽  
Functional Consequences ◽  
Sensory Responses ◽  
First Year Of Life ◽  
Methionyl Trna Synthetase

Background: Methionyl-tRNA synthetase (MARS) links methionine to its cognate tRNA required for translation. MARS mutations have been linked to adult-onset CMT2U. Methods: The proband had weakness in her first year of life, sitting at 11 months and walking at 20 months old. At 4 years old she was areflexic with distal > proximal weakness. Nerve conduction studies showed normal median and sural sensory responses with absent common peroneal, low median and tibial motor amplitudes. EMG noted denervation and quadriceps biopsy revealed neurogenic atrophy. Genetic testing for spinal muscular atrophy and sequencing of MNF2, RAB7A, LMNA, MPZ, HSPB1, NEFL, GADP1, TRPV4, HSPB8, GJB1 and PLEK8G5 were negative. She stopped walking at 9 years old and could not raise her arms above her head at 11 years old. Results: Exome sequencing identified MARS: c.1189G>A; p.Ala397Thr. To determine the functional consequences of p.A397T-MARS, yeast complementation assays were performed. Wild type or mutant MARS were cloned into yeast lacking the endogenous MARS ortholog. Wild-type MARS supported robust cellular growth, while the p.A397T-MARS insert did not support cellular growth confirming deleterious effect of this variant. Conclusions: Our patient’s phenotype was similar to children with motor-predominant GARS mutations. Functional data notes this MARS variant to be damaging and predictive of a severe, early-onset phenotype.

scholarly journals KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3242-3261 ◽  
Author(s):  
Laura Cif ◽  
Diane Demailly ◽  
Jean-Pierre Lin ◽  
Katy E Barwick ◽  
Mario Sa ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Early Onset ◽  
Rating Scales ◽  
Study Cohort ◽  
Related Disease ◽  
Status Dystonicus ◽  
Deep Brain

Abstract Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5–37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke Fahn Marsden’s Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002 and P = 0.012). At 1 year post-deep brain stimulation, >50% of subjects showed BFMDRS-M and BFMDRS-D improvements of >30%. In the long-term deep brain stimulation cohort (deep brain stimulation inserted for >5 years, n = 8), improvement of >30% was maintained in 5/8 and 3/8 subjects for the BFMDRS-M and BFMDRS-D, respectively. The greatest BFMDRS-M improvements were observed for trunk (53.2%) and cervical (50.5%) dystonia, with less clinical impact on laryngeal dystonia. Improvements in gait dystonia decreased from 20.9% at 1 year to 16.2% at last assessment; no patient maintained a fully independent gait. Reduction of BFMDRS-D was maintained for swallowing (52.9%). Five patients developed mild parkinsonism following deep brain stimulation. KMT2B-related disease comprises an expanding continuum from infancy to adulthood, with early evidence of genotype-phenotype correlations. Except for laryngeal dysphonia, deep brain stimulation provides a significant improvement in quality of life and function with sustained clinical benefit depending on symptoms distribution.

Association of vitamin D receptor genotypes with early onset rheumatoid arthritis

2001 ◽  
Vol 28 (1) ◽  
pp. 89-93 ◽  
Author(s):  
J. R. Garcia-Lozano ◽  
M. F. Gonzalez-Escribano ◽  
A. Valenzuela ◽  
A. Garcia ◽  
A. Nunez-Roldan
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Early Onset

Outcome of infants with unilateral Sturge-Weber syndrome and early onset seizures

2000 ◽  
Vol 42 (11) ◽  
pp. 756-759 ◽  
Author(s):  
Uri Kramer ◽  
Esther Kahana ◽  
Zamir Shorer ◽  
Bruria Ben-Zeev
Keyword(s):  
Early Onset ◽  
Weber Syndrome ◽  
Sturge Weber Syndrome
Sign in / Sign up

Export Citation Format

Share Document