Publications by authors named "L Bastaki"

31 Publications

[When all roads lead to Africa…].

Med Sci (Paris) 2019 Nov 20;35 Hors série n° 2:15-17. Epub 2019 Dec 20.

Kuwait Medical Genetic Centre, Kuwait.

Congenital myopathies represent a quite heterogeneous group of neuromuscular disorders both at the clinical and genetic level. High-throughput sequencing (NGS), targeted or not, combined with muscle pathology, greatly facilitate their accurate characterization and occasionally lead to unexpected discoveries like in the case reported here in a Kuwaiti family facing a long diagnostic odyssey.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1051/medsci/2019237DOI Listing
November 2019

Recurrent homozygous damaging mutation in , encoding a protein disulfide isomerase, in four families with microlissencephaly.

J Med Genet 2020 04 5;57(4):274-282. Epub 2019 Oct 5.

Rady Children's Institute for Genomic Medicine, San Diego, California, USA

Background: Protein disulfide isomerase (PDI) proteins are part of the thioredoxin protein superfamily. PDIs are involved in the formation and rearrangement of disulfide bonds between cysteine residues during protein folding in the endoplasmic reticulum and are implicated in stress response pathways.

Methods: Eight children from four consanguineous families residing in distinct geographies within the Middle East and Central Asia were recruited for study. All probands showed structurally similar microcephaly with lissencephaly (microlissencephaly) brain malformations. DNA samples from each family underwent whole exome sequencing, assessment for repeat expansions and confirmatory segregation analysis.

Results: An identical homozygous variant in (c.500G>A), encoding thioredoxin-related transmembrane protein 2, segregated with disease in all four families. This variant changed the last coding base of exon 6, and impacted mRNA stability. All patients presented with microlissencephaly, global developmental delay, intellectual disability and epilepsy. While is an activator of cellular repeat expansion toxicity, patients showed no evidence of repeat expansions.

Conclusion: The c.500G>A allele associates with recessive microlissencephaly, and patients show no evidence of expansions. is the first PDI implicated in a recessive disease, suggesting a protein isomerisation defect in microlissencephaly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jmedgenet-2019-106409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405652PMC
April 2020

Current management of Duchenne muscular dystrophy in the Middle East: expert report.

Neurodegener Dis Manag 2019 06 5;9(3):123-133. Epub 2019 Jun 5.

Unidad de Patología Neuromuscular Servicio de Neurología, Hospital Sant Joan de Déu, Barcelona, Spain.

Duchenne muscular dystrophy (DMD) is a severe and rare X-linked neuromuscular childhood disorder that results in functional decline, loss of ambulation and early death due to cardiac or respiratory failure. The objective of this paper is to address different aspects of the current management of DMD in the Middle East, north Africa (MENA) region, and to gather experts' recommendations on how to optimally diagnose and treat patients suffering from this disease. A group of experts (neuromuscular medicine, neuropediatricians and geneticists) convened to discuss the diagnosis and management of DMD in the MENA region. A list of practical statements was prepared by the chair of the meeting to guide the discussions around critical aspects relating to the current and future management of DMD. Ideally, DMD management should be a multidisciplinary approach. Nevertheless, few tertiary care hospitals in the region are currently able to provide the full spectrum of medical expertise and services needed by DMD patients. Clinical practice in the region remains heterogeneous. Specific guidelines for diagnosis and treatment are needed in the MENA region to improve outcomes. Disease awareness among the general public and the medical community is lacking. Now that mutation-specific therapies are being developed and more widely studied, general education programs regarding early signs and symptoms, a standardized referral and diagnosis pathway, patient registries and support groups will significantly improve the management of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/nmt-2019-0002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609894PMC
June 2019

GNE myopathy in the bedouin population of Kuwait: Genetics, prevalence, and clinical description.

Muscle Nerve 2018 11 3;58(5):700-707. Epub 2018 Oct 3.

Kuwait Medical Genetics Centre, Sabah Health District, Shuwaikh, Kuwait.

Introduction: GNE myopathy is a rare recessive myopathy caused by mutations in the GNE gene. It is mainly a distal myopathy with relative sparing of the quadriceps muscle.

Methods: Patients with distal myopathies from Kuwait were examined and tested for the Middle Eastern GNE gene founder mutation, p.M743T. Patients were further studied for disease-associated features.

Results: GNE myopathy was confirmed in 14 of the 37 patients (37.8%) screened. All cases were caused by the p.M743T mutation. Age of onset and time from disease onset to loss of ambulation were variable. Both wasted and hypertrophied calf muscles were noted. Severely affected quadriceps were present in 1 patient, and ptosis, ophthalmoplegia, and tongue wasting in another.

Discussion: The scope of the p.M743T mutation now includes the Arabian Peninsula. Variations in age of onset, disease progression, and distribution in patients harboring the same mutation suggest the role of other genetic- and environment-modifying factors. Muscle Nerve 58: 700-707, 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mus.26337DOI Listing
November 2018

STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility.

Hum Mutat 2018 12 11;39(12):1980-1994. Epub 2018 Oct 11.

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK.

SH3 and cysteine-rich domain-containing protein 3 (STAC3) is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery, though its role and function are not yet completely understood. Here, we report 18 patients carrying a homozygous p.(Trp284Ser) STAC3 variant in addition to a patient compound heterozygous for the p.(Trp284Ser) and a novel splice site change (c.997-1G > T). Clinical severity ranged from prenatal onset with severe features at birth, to a milder and slowly progressive congenital myopathy phenotype. A malignant hyperthermia (MH)-like reaction had occurred in several patients. The functional analysis demonstrated impaired ECC. In particular, KCl-induced membrane depolarization resulted in significantly reduced sarcoplasmic reticulum Ca release. Co-immunoprecipitation of STAC3 with Ca 1.1 in patients and control muscle samples showed that the protein interaction between STAC3 and Ca 1.1 was not significantly affected by the STAC3 variants. This study demonstrates that STAC3 gene analysis should be included in the diagnostic work up of patients of any ethnicity presenting with congenital myopathy, in particular if a history of MH-like episodes is reported. While the precise pathomechanism remains to be elucidated, our functional characterization of STAC3 variants revealed that defective ECC is not a result of Ca 1.1 sarcolemma mislocalization or impaired STAC3-Ca 1.1 interaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23635DOI Listing
December 2018