| 1. |
- Régal, Luc, et al.
(författare)
-
PREPL deficiency : Delineation of the phenotype and development of a functional blood assay
- 2018
-
Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600. ; 20:1, s. 109-118
-
Tidskriftsartikel (refereegranskat)abstract
- PurposePREPL deficiency causes neonatal hypotonia, ptosis, neonatal feeding difficulties, childhood obesity, xerostomia, and growth hormone deficiency. Different recessive contiguous gene deletion syndromes involving PREPL and a variable combination of SLC3A1 (hypotonia-cystinuria syndrome), CAMKMT (atypical hypotonia-cystinuria syndrome), and PPM1B (2p21 deletion syndrome) have been described. In isolated PREPL deficiency, previously described only once, the absence of cystinuria complicates the diagnosis. Therefore, we developed a PREPL blood assay and further delineated the phenotype.MethodsClinical features of new subjects with PREPL deficiency were recorded. The presence of PREPL in lymphocytes and its reactivity with an activity-based probe were evaluated by western blot.ResultsFive subjects with isolated PREPL deficiency, three with hypotonia-cystinuria syndrome, and two with atypical hypotonia-cystinuria syndrome had nine novel alleles. Their IQs ranged from 64 to 112. Adult neuromuscular signs included ptosis, nasal dysarthria, facial weakness, and variable proximal and neck flexor weakness. Autonomic features are prevalent. PREPL protein and reactivity were absent in lymphocytes from subjects with PREPL deficiency, but normal in the clinically similar Prader-Willi syndrome.ConclusionPREPL deficiency causes neuromuscular, autonomic, cognitive, endocrine, and dysmorphic clinical features. PREPL is not deficient in Prader-Willi syndrome. The novel blood test should facilitate the confirmation of PREPL deficiency.
|
|
| 2. |
- Oldfors Hedberg, Carola, 1969, et al.
(författare)
-
A new early-onset neuromuscular disorder associated with kyphoscoliosis peptidase (KY) deficiency.
- 2016
-
Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 24:12, s. 1771-1777
-
Tidskriftsartikel (refereegranskat)abstract
- We describe a new early-onset neuromuscular disorder due to a homozygous loss-of-function variant in the kyphoscoliosis peptidase gene (KY). A 7.5-year-old girl with walking difficulties from 2 years of age presented with generalized muscle weakness; mild contractures in the shoulders, hips and feet; cavus feet; and lordosis but no scoliosis. She had previously been operated with Achilles tendon elongation. Whole-body MRI showed atrophy and fatty infiltration in the calf muscles. Biopsy of the vastus lateralis muscle showed variability in fiber size, with some internalized nuclei and numerous very small fibers with variable expression of developmental myosin heavy chain isoforms. Some small fibers showed abnormal sarcomeres with thickened Z-discs and small nemaline rods. Whole-exome sequencing revealed a homozygous one-base deletion (c.1071delG, p.(Thr358Leufs*3)) in KY, predicted to result in a truncated protein. Analysis of an RNA panel showed that KY is predominantly expressed in skeletal muscle in humans. A recessive variant in the murine ortholog Ky was previously described in a spontaneously generated mouse mutant with kyphoscoliosis, which developed postnatally and was caused by dystrophy of postural muscles. The abnormal distribution of Xin and Ky-binding partner filamin C in the muscle fibers of our patient was highly similar to their altered localization in ky/ky mouse muscle fibers. We describe the first human case of disease associated with KY inactivation. As in the mouse model, the affected child showed a neuromuscular disorder - but in contrast, no kyphoscoliosis.
|
|
| 3. |
- OLSSON, M, et al.
(författare)
-
EROSION-CORROSION CHARACTERISTICS OF A 2.25 CR-1 MO STEEL EXPOSED AT LOW PARTICLE VELOCITIES
- 1995
-
Ingår i: TRIBOLOGY INTERNATIONAL. - : BUTTERWORTH-HEINEMANN LTD. - 0301-679X. ; 28:2, s. 107-117
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The erosion-corrosion characteristics of a 2.25 Cr-1 Mo steel at low particle velocities and elevated temperatures were determined using a nozzle type laboratory erosion tester. The tests were performed with 180-360 mu m angular alumina particles at 60 de
|
|
| 4. |
- Savvidou, Antri, et al.
(författare)
-
Drug-induced hyperthermia with rhabdomyolysis in CLN3 disease
- 2022
-
Ingår i: European Journal of Paediatric Neurology. - : Elsevier BV. - 1090-3798 .- 1532-2130. ; 39, s. 74-78
-
Tidskriftsartikel (refereegranskat)abstract
- CLN3 disease (MIM# 204200), the most prevalent of the neuronal ceroid lipofuscinoses (NCL), is an autosomal recessive disorder with juvenile onset characterized by blindness, epilepsy, dementia, psychiatric manifestations, and motor deterioration. Problems related to behavior, emotions and thought are among the main features. Antidepressant and antipsychotic drugs have been employed with variable results. Neuroleptic malignant syndrome (NMS) has previously been described in two patients with NCL, one with CLN3 disease and one with adult onset NCL of unclear genetic origin. Our aims were to describe the occurrence of drug-induced hyperthermia in pediatric patients with CLN3 disease from West and South Sweden and to delineate the range of associated clinical features. Our study identified four patients presenting with seven episodes of severe drug-induced hyperthermia and either NMS-like or Serotonin syndrome (SS)-like features. Possibly provoking drugs were risperidone, clozapine, olanzapine, haloperidol, quetiapine, and sertraline. The course was atypical, frequently prolonged, associated with rhabdomyolysis and status dystonicus, and resulted in the death of three of the patients. Our study points to a vulnerability to drug-induced hyperthermia in patients with CLN3 disease which we believe could be underreported. Interestingly the proposed pathophysiological mechanisms behind NMS and SS on one hand and CLN3 on the other hand seem to converge in a common mechanism involving dysregulation of the sympathetic nervous system.
|
|
