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Edition of 15 September 2023

New Syndromes

HMGCR mutations cause an autosomal-recessive progressive limb-girdle muscular dystrophy

A new study published in the American Journal of Human Genetics identified bi-allelic variants in HMGCR (implied in statins targeting) who express unexplained limb-girdle like muscular dystrophy. Clinical features are incidental high CPK levels, proximal muscle weakness, variable age of onset, and progression leading to impaired ambulation. Various analyses (histopathological, biopsies and molecular modeling) show that individuals with bi-allelic amorphic (i.e., null and/or hypomorphic) variants in HMGCR display phenotypes that resemble non-genetic causes of myopathy involving this reductase. The study expands knowledge regarding the mechanisms leading to muscular dystrophy through dysregulation of the mevalonate pathway, autoimmune myopathy, and statin-induced myopathy.

To read more about “Autosomal recessive limb-girdle muscular dystrophy”

Am J Hum Genet . 2023 Jun 1;110(6):989-997

SRSF1 haploinsufficiency is responsible for a syndromic developmental disorder associated with intellectual disability

A new study published in the American Journal of Human Genetics identified bi-allelic heterozygous germline SRSF1 variants (a non-snRNP involved in constitutive and alternative splicing), within 17 individuals (10 females and 7 males) who express recurrent phenotype including developmental delay and intellectual disability (DD/ID), hypotonia, neurobehavioral problems, with variable skeletal (66.7%) and cardiac (46%) anomalies. Various analyses (in silico structural modelling, in vivo splicing assay in Drosophila, an episignature analysis in blood-derived DNA) show that haploinsufficiency of SRSF1 is responsible for a syndromic NDD with ID due to a partial loss of SRSF1-mediated splicing activity.

Am J Hum Genet . 2023 May 4;110(5):790-808

ADAMTS15 mutations cause a novel form of distal arthrogryposis

A new study published in Genetics in Medicine identified bi-allelic variants of ADAMTS15, within 5 affected individuals (from 4 unrelated consanguineous families) who express congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. Various analyses (on single-cell level during murine embryogenesis, in situ hybridization and RNAscope, radiography) provide evidence that these variants cause a novel autosomal recessive connective tissue disorder, resulting in a distal arthrogryposis syndrome.

Genet Med . 2022 Oct;24(10):2187-2193

Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature

A new study published in Genetics in Medicine identified mono-allelic variants in KDM2B (which encore an epigenetic regulator), within 27 individuals who express developmental delay and/or intellectual disability; autism; attention deficit disorder/attention deficit hyperactivity disorder; congenital organ anomalies mainly of the heart, eyes, and urogenital system; and subtle facial dysmorphism. Methylation arrays on peripheral blood DNA samples provide evidence that most of these variants (a mutational hotspot) are associated with NDD (neurodevelopment disorders) and a specific epigenetic signature detectable in peripheral blood.

Genet Med . 2023 Jan;25(1):49-62

New Genes

Familial temporal lobe epilepsy : Novel NALCN variant linked to temporal lobe epilepsy

To read more about “Familial temporal lobe epilepsy”

Am J Med Genet A . 2023 Jul;191(7):1942-1947

Clustered variants in the 5′ coding region of TRA2B cause a distinctive neurodevelopmental syndrome

Genet Med . 2023 Apr;25(4):100003

PCD (Primary ciliary dyskinesia) : Pathogenic variants in CLXN encoding the outer dynein arm docking–associated calcium-binding protein calaxin cause PCD

To read more about “Primary ciliary dyskinesia”

Genet Med . 2023 May;25(5):100798

Cleidocranial dysplasia : Heterozygous pathogenic variants involving CBFB cause a new skeletal disorder resembling cleidocranial dysplasia

To read more about “Cleidocranial dysplasia”

J Med Genet . 2023 May;60(5):498-504

Clinical Research

TANGO2 deficiency disorder : Natural history... baseline assessment of 73 patients

Pour en savoir plus

To read more about “Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome”

Genet Med . 2023 Apr;25(4):100352

ALG13-CDG : Long‐term outcomes

To read more about “ALG13-CDG”

Am J Med Genet A . 2023 Jun;191(6):1626-1631

Birt-Hogg-Dubé syndrome : Exons 1–3 deletion in FLCN is associated with increased risk of pneumothorax in Chine

To read more about “Birt-Hogg-Dubé syndrome”

Orphanet J Rare Dis . 2023 May 12;18(1):115

Neurofibromatosis type 1 : French cohort of children and adolescents with symptomatic inoperable plexiform neurofibromas... CASSIOPEA study

To read more about “Neurofibromatosis type 1”

Eur J Med Genet . 2023 May;66(5):104734

HHT (Hereditary hemorrhagic telangiectasia) : Brain Abscess and Stroke in Children and Adults... analysis of a Large National Claims Database

To read more about “Hereditary hemorrhagic telangiectasia”

Neurology . 2023 Jun 6;100(23):e2324-e2330

ALS (Amyotrophic lateral sclerosis) : Frequency of euthanasia and other end-of-life practices, associated factors, and quality of end-of-life care, in the Netherlands... a population-based study

To read more about “Amyotrophic lateral sclerosis”

Lancet Neurol . 2023 Jul;22(7):591-601

Myasthenia gravis : Physician ‑ and patient ‑ reported perspectives in Europe... a real ‑ world survey

To read more about “Myasthenia gravis”

Orphanet J Rare Dis . 2023 Jun 29;18(1):169

Multiple myeloma, relapsed & refractory : Ide-cel or Standard Regimens

To read more about “Multiple myeloma”

N Engl J Med . 2023 Mar 16;388(11):1002-1014

SHML (Rosaï-Dorfman disease) : The value of 18F-FDG PET/CT in the systemic evaluation of patients... retrospective study and literature review

To read more about “Rosaï-Dorfman disease”

Orphanet J Rare Dis . 2023 May 13;18(1):116

Cumulative burden of late, major surgical intervention in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study (CCSS) cohort

Lancet Oncol . 2023 Jun;24(6):691-700

PKU (Phenylketonuria) : Aspartame... an analysis of the daily phenylalanine intake of aspartame-containing drugs marketed in France

To read more about “Phenylketonuria”

Orphanet J Rare Dis . 2023 Jun 8;18(1):142

Multiple myeloma : Phase 3, Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma... a randomized trial

To read more about “Multiple myeloma”

Nat Med . 2023 Apr;29(4):869-879

Huntington disease : Phase 3, safety and efficacy of valbenazine for the treatment of chorea... KINECT-HD, randomised, double-blind, placebo-controlled trial

To read more about “Huntington disease”

Lancet Neurol . 2023 Jun;22(6):494-504

Von Willebrand disease type 3 : Phase 3, Prophylaxis with recombinant von Willebrand factor ( rVWF )... results of a post hoc analysis

To read more about “Von Willebrand disease type 3”

Eur J Haematol . 2023 Jul;111(1):29-40

DLBCL (Diffuse large B-cell lymphoma) : Phase 3, Polatuzumab vedotin in previously untreated disease... an Asia subpopulation analysis from the POLARIX trial

To read more about “Diffuse large B-cell lymphoma”

Blood . 2023 Apr 20;141(16):1971-1981

Squamous cell carcinoma of the esophagus, advanced or metastatic : Phase 3, Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment ... RATIONALE-306, a global, randomised, placebo-controlled, study

To read more about “Squamous cell carcinoma of the esophagus”

Lancet Oncol . 2023 May;24(5):483-495

Prader-Willi syndrome : Phase 3, Diazoxide Choline Extended-Release Tablet... a double-Blind, Placebo-Controlled Trial

To read more about “Prader-Willi syndrome”

J Clin Endocrinol Metab . 2023 Jun 16;108(7):1676-1685

Adenocarcinoma of the esophagus, locally advanced : Phase 3, Zolbetuximab + mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated & unresectable... SPOTLIGHT, a multicentre, randomised, double-blind, trial

To read more about “Adenocarcinoma of the esophagus”

Lancet . 2023 May 20;401(10389):1655-1668

Gaucher disease type 1 : Phase 3 & 2, Long-term effects of eliglustat on skeletal manifestations in clinical trials

To read more about “Gaucher disease type 1”

Genet Med . 2023 Feb;25(2):100329

Craniopharyngioma : Phase 2, Proton therapy and limited surgery for paediatric and adolescent patients.... RT2CR, a single-arm study

To read more about “Craniopharyngioma”

Lancet Oncol . 2023 May;24(5):523-534

Pompe, infantile onset (GSD type 2) : Phase 2, safety and efficacy of avalglucosidase alfa... open-label Mini-COMET study, 6-month primary analysis report

To read more about “Glycogen storage disease due to acid maltase deficiency, infantile onset”

Genet Med . 2023 Feb;25(2):100328

Rare cancers : Phase 2, Dabrafenib plus trametinib in BRAFV600E mutation... ROAR trial

Nat Med . 2023 May;29(5):1103-1112

Myasthenia gravis : Phase 1b / 2a, safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in a non-randomised study

To read more about “Myasthenia gravis”

Lancet Neurol . 2023 Jul;22(7):578-590

ALS (Amyotrophic lateral sclerosis) : Respiratory Strength Training... A Double-Blind, Randomized, Multicenter, Sham-Controlled Trial

To read more about “Amyotrophic lateral sclerosis”

Neurology . 2023 Apr 11;100(15):e1634-e1642

HCC (Hepatocellular carcinoma) : Clinical practice guidelines and real-life practice... a japanese perspective

To read more about “Hepatocellular carcinoma”

Clin Mol Hepatol . 2023 Apr;29(2):242-251

HGPS (Hutchinson-Gilford progeria syndrome) : FDA approval summary for lonafarnib (Zokinvy) for the treatment of processing-deficient progeroid laminopathies

To read more about “Hutchinson-Gilford progeria syndrome”

Genet Med . 2023 Feb;25(2):100335

AML & MDS (Acute myeloid leukemia & Myelodysplastic syndrome) : Ipilimumab plus decitabine for post-transplant or transplant naïve settings

To read more about “Acute myeloid leukemia”
To read more about “Myelodysplastic syndrome”

Blood . 2023 Apr 13;141(15):1884-1888

Congenital IGHD (Non-acquired isolated growth hormone deficiency) : Sex Differences in Long-Term Safety and Tolerability of GH Replacement Therapy in Adults

To read more about “Non-acquired isolated growth hormone deficiency”

J Clin Endocrinol Metab . 2023 Jun 16;108(7):e415-e424

OI (Osteogenesis imperfecta) : Pharmacological Therapies for Fracture Risk Reduction in Adults

To read more about “Osteogenesis imperfecta”

J Clin Endocrinol Metab . 2023 Jun 16;108(7):1787-1796

PFAPA syndrome : Tonsillectomy reduces the family impact of the syndrome and improves health-related quality of life in affected children

To read more about “PFAPA syndrome”

Orphanet J Rare Dis . 2023 Jun 20;18(1):153

Primary cutaneous T-cell lymphoma, refractory : CD38 Targeting in Aggressive cancers

To read more about “Primary cutaneous T-cell lymphoma”

J Invest Dermatol . 2023 Jul;143(7):1329-1332.e3

Pompe (Glycogen storage disease due to acid maltase deficiency) : Home-based enzyme replacement therapy in children and adults, a prospective study

To read more about “Glycogen storage disease due to acid maltase deficiency”

Orphanet J Rare Dis . 2023 May 8;18(1):108

NMOSD (Neuromyelitis optica spectrum disorder) : Ravulizumab in Aquaporin‐4 positive

To read more about “Neuromyelitis optica spectrum disorder”

Ann Neurol . 2023 Jun;93(6):1053-1068

PHN (Paroxysmal nocturnal hemoglobinuria) : Long-term outcomes of patients treated with eculizumab in a real-world setting

To read more about “Paroxysmal nocturnal hemoglobinuria”

Eur J Haematol . 2023 Jul;111(1):84-95

Vascular anomaly or angioma : Oral antibiotic prophylaxis for infection in patients receiving sirolimus treatment... a multicenter retrospective study

To read more about “Vascular anomaly or angioma”

Orphanet J Rare Dis . 2023 May 24;18(1):121

Nasopharyngeal carcinoma : Role of chemotherapy in patients treated with radiotherapy... MAC-NPC, an updated individual patient data network meta-analysis.

To read more about “Nasopharyngeal carcinoma”

Lancet Oncol . 2023 Jun;24(6):611-623

Therapeutic Approaches

MJD (Spinocerebellar ataxia type 3) : Extracellular vesicle-based delivery of silencing sequences

To read more about “Spinocerebellar ataxia type 3”

Mol Ther . 2023 May 3;31(5):1275-1292

Citrin deficiency : Nicotinamide riboside rescues dysregulated glycolysis and fatty acid β-oxidation in a human hepatic cell model

To read more about “Citrin deficiency”

Hum Mol Genet . 2023 May 18;32(11):1922-1931

Infantile hypophosphatasia : Prenatal asfotase alfa-mediated enzyme replacement therapy restores delayed calcification in model mice

To read more about “Infantile hypophosphatasia”

Eur J Med Genet . 2023 Jul;66(7):104787

SMA (Proximal spinal muscular atrophy) : Potentiation of neuromuscular transmission by a small molecule calcium channel gating modifier improves motor function in mouse model

To read more about “Proximal spinal muscular atrophy”

Hum Mol Genet . 2023 May 18;32(11):1901-1911

BTHS (Barth syndrome) : Genetic modifiers modulate phenotypic expression of tafazzin deficiency in a mouse model

To read more about “Barth syndrome”

Hum Mol Genet . 2023 Jun 5;32(12):2055-2067

Multiple myeloma : In vivo bone marrow microenvironment siRNA delivery using lipid–polymer nanoparticles

To read more about “Multiple myeloma”

Proc Natl Acad Sci U S A . 2023 Jun 20;120(25):e2215711120

Diagnostic Approaches

Classic glucose transporter type 1 deficiency syndrome : Prospective Multicenter Validation of a Simple Blood Test

To read more about “Classic glucose transporter type 1 deficiency syndrome”

Neurology . 2023 Jun 6;100(23):e2360-e2373

Barrett esophagus : High-grade dysplasia & Estimated Burden of Screening in the United States

To read more about “High-grade dysplasia in patients with Barrett esophagus”

Gastroenterology . 2023 Jul;165(1):283-285.e2

Neonatal screening

Expanding the Australian Newborn Blood Spot Screening Program using genomic sequencing: do we want it and are we ready?

Eur J Hum Genet . 2023 Jun;31(6):703-711

Patient Management and Therapy

DLBCL (Diffuse large B-cell lymphoma) : How I treat Elderly Patients in the frontline setting

To read more about “Diffuse large B-cell lymphoma”

Blood . 2023 May 25;141(21):2566-2575

Childhood cancer : A joint international consensus statement for measuring quality of survival

Nat Med . 2023 Jun;29(6):1340-1348

Cardiac sarcoidosis : Phenotypes, diagnosis, treatment, and prognosis

To read more about “Sarcoidosis”

Eur Heart J . 2023 May 1;44(17):1495-1510

The epidemiology, clinical presentation and treatment outcomes in CNS actinomycosis: a systematic review of reported cases

To read more about “Actinomycosis”

Orphanet J Rare Dis . 2023 Jun 2;18(1):133

AML (Acute myeloid leukemia) : How I Treat in 2023... incorporating the Updated Classifications and Guidelines

To read more about “Acute myeloid leukemia”

Blood . 2023 Jun 8;141(23):2813-2823

Recommendations

Phelan-McDermid (Monosomy 22q13.3) : Consensus recommendations on counselling with special attention to recurrence risk and to ring chromosome 22

To read more about “Monosomy 22q13.3”

Eur J Med Genet . 2023 Jul;66(7):104773

Phelan-McDermid (Monosomy 22q13.3) : European Journal of Medical Genetics Consensus recommendations on organization of care

To read more about “Monosomy 22q13.3”

Eur J Med Genet . 2023 Jul;66(7):104747

Uterine sarcomas: clinical practice guidelines for diagnosis, treatment, and follow-up, by Spanish group for research on sarcomas (GEIS)

To read more about “Carcinosarcoma of the corpus uteri”

Ther Adv Med Oncol . 2023 Mar 28;15:17588359231157645

Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network

To read more about “Multiple myeloma”

Lancet Oncol . 2023 Jun;24(6):e255-e269

Juvenile idiopathic arthritis : New and updated recommendations for the treatment of JIA associated uveitis and idiopathic chronic anterior uveitis

To read more about “Juvenile idiopathic arthritis”

Arthritis Care Res (Hoboken) . 2023 May;75(5):975-982

Fetal chromosome abnormalities : Noninvasive prenatal screening (NIPS) in a general-risk population... an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)

Genet Med . 2023 Feb;25(2):100336

SLE (Systemic lupus erythematosus) : Evaluation of the EULAR /American College of Rheumatology Classification Criteria in a Population‐Based Registry

To read more about “Systemic lupus erythematosus”

Arthritis Care Res (Hoboken) . 2023 May;75(5):1007-1016

PKU (Phenylketonuria) : Nutrition management of PKU with pegvaliase therapy... update of the web-based PKU nutrition management guideline recommendations

To read more about “Phenylketonuria”

Orphanet J Rare Dis . 2023 Jun 22;18(1):155

Quality of Life

Rare thyroid carcinoma : Health-Related Quality of Life at Diagnosis for Pediatric Thyroid Cancer Patients

To read more about “Rare thyroid carcinoma”

J Clin Endocrinol Metab . 2023 Apr 13;108(5):e169-e177

Health-related quality of life in patients with β-thalassemia: Data from the phase 3 BELIEVE trial of luspatercept

To read more about “Beta-thalassemia”

Eur J Haematol . 2023 Jul;111(1):113-124

SLE (Systemic lupus erythematosus) : High prevalence but low impact of cognitive dysfunction on quality of life in patients with lupus and neuropsychiatric symptoms

To read more about “Systemic lupus erythematosus”

Arthritis Care Res (Hoboken) . 2023 May;75(5):1017-1025

Other news

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Summary of the edition of 15 September 2023

Editorial
- Editorial
- ERN News
Political news
Scientific news
And also...