Summary

Back to summary

Editorial
Political news
Scientific news
And also...

Share:

Edition of 19 December 2024

New Syndromes

RFC4 variants cause a multisystemic disorder which partially overlaps with CANVAS

A new study published in American Journal of Human Genetics described bi-allelic loss-of-function variants in RFC4, which encodes a subunit of the replication factor C (RFC) complex required for DNA replication, and consequently for genomic integrity and cellular division. The variants were found among 9 individuals from 8 unrelated families, presenting with a multisystemic disorder of variable severity and age at onset. The disorder was characterized by a clinical spectrum of incoordination and muscle weakness, hearing impairment, and decreased body weight. Various analyses identified RFC4 mutations as expanding the genetic and phenotypic landscape of RFC-related disorders. Futher pathophysiological information revealed that RFC4 mutations resulted in decreased formation and stability of RFC complex affecting in fine DNA replication and cell cycle progression.

Am J Hum Genet . 2024 Sep 5;111(9):1970-1993

SREBF2 variants cause dermatologic, neurologic, and skeletal defects

A new study published in Genetics in Medecine characterized heterozygous de novo variants in SREBF2, which belongs to a family of genes encoding transcription factors for lipogenic genes as key factors in the regulation of fatty acid synthesis during a low-fat diet. The variants were found among 2 unrelated individuals affected by complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes (complex dermatological, neurological and skeletal abnormalities). Various analyses identified SREBF2 as an additional gene associated with SREBP-related complex disorders and expand the phenotypic spectrum of this disorder. Futher pathophysiological information revealed that SREBF2 mutations resulted in impaired site 1 protease (S1P) cleavage motif limited the cleavage of its targets, including SREBP2 transcription factor itself.

Genet Med. 2024 Sep;26(9):101174. doi: 10.1016/j.gim.2024

ZNRF3 variants cause various phenotypes according to genotype-phenotype correlations

A new study published in American Journal of Human Genetics characterized germline variants in ZNRF3, which encodes a negative-feedback regulator of Wnt/β-catenin signaling playing an important role in human brain development. The variants were found among 12 unrelated individuals affected by various phenotypes correlated with different genotypes. Some patients suffered from a variety of non-neurodevelopmental disorder (NDD) phenotypes (including heart, adrenal, or nephrotic problems) but most presented an NDD phenotype with micro or macrocephaly suprisely. Various analyses emphasized the role of ZNRF3 via the Wnt/b-catenin signaling in regulating proper human brain size during neurogenesis. Futher pathophysiological information revealed that ZNRF3 mutations resulted in mirror brain phenotypes through opposite mechanisms via Wnt/β-catenin signaling in a protein domain-dependent fashion.

Am J Hum Genet. 2024 Sep 5;111(9):1994-2011

New Genes

Rare non-syndromic intellectual disability: Identification of heterozygous variants in PSMC5

To read more about “Rare non-syndromic intellectual disability”

Hum Mol Genet. 2024 Aug 18;33(17):1506-1523

Retinitis pigmentosa: Identification of heterozygous and homozygous variants in TMEM216

To read more about “Retinitis pigmentosa”

Am J Hum Genet. 2024 Sep 5;111(9):2012-2030

Clinical Research

Familial steroid-resistant nephrotic syndrome with adrenal insufficiency: Natural history to identify factors influencing survival in subjects (retrospective cross-sectional study)

To read more about “Familial steroid-resistant nephrotic syndrome with adrenal insufficiency”

Orphanet J Rare Dis. 2024 Sep 27;19(1):355

Phenylketonuria: Bone mineral density-related outcomes experienced by adults on a phenylalanine-restricted diet (systemic review and meta-analysis)

To read more about “Phenylketonuria”

Orphanet J Rare Dis. 2024 Sep 12;19(1):338

Pheochromocytoma-paraganglioma (PPGLs): Pathogenic succinate dehydrogenase type B variant carriers’ outcomes for risk assessment and early detection of PPGLs (systemic review and meta-analysis)

To read more about “Pheochromocytoma-paraganglioma”

J Clin Endocrinol Metab. 2024 Aug 13;109(9):2400-2410

Systemic lupus erythematosus: Effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (systemic review and meta-analysis)

To read more about “Systemic lupus erythematosus”

Arthritis Rheumatol . 2024 Sep;76(9):1408-1418

Early-onset autosomal dominant Alzheimer disease: Clinical features, γ-secretase activity and biomarker trajectories in carriers of pathogenic PSEN1 variants (retrospective observational study)

To read more about “Early-onset autosomal dominant Alzheimer disease”

Lancet Neurol. 2024 Sep;23(9):913-924

Hemophilia A: Clinical and molecular characteristics of affected individuals and carriers (retrospective observational review)

To read more about “Hemophilia A”

Am J Med Genet A. 2024 Sep;194(9):e63657

Medullary thyroid carcinoma: Clinical presentations and long-term outcomes of children and young adults (retrospective cohort study)

To read more about “Medullary thyroid carcinoma”

J Clin Endocrinol Metab. 2024 Aug 13;109(9):2256-2268

Progressive familial intrahepatic cholestasis type 4: Clinical outcomes and genotype-phenotype correlation in children (retrospective analysis of clinical registry data)

To read more about “Progressive familial intrahepatic cholestasis type 4”

Hepatology. 2024 Sep 1;80(3):511-526

Prolactinoma: Clinical features and medication/surgery outcomes in children and adolescents (retospective cohort study)

To read more about “Prolactinoma”

J Clin Endocrinol Metab. 2024 Aug 13;109(9):e1741-e1749

Amyotrophic lateral sclerosis: Promising modulating effect of apillimod dimesylate on pharmacodynamic target engagement biomarkers after confirmed CNS penetrance (phase 2 trial)

To read more about “Amyotrophic lateral sclerosis”

Brain. 2024 Sep 3;147(9):2998-3008

Anti-neutrophil cytoplasmic antibody-associated vasculitis: Absence of effect on relapse risk with plasma exchange or initial glucocorticoid tapering regimen (post hoc analysis of phase 3 trial)

To read more about “Anti-neutrophil cytoplasmic antibody-associated vasculitis”

Arthritis Rheumatol. 2024 Sep;76(9):1431-1438

Ataxia-telangiectasia: Absence of neurological symptom improvement in children with intra-erythrocyte dexamethasone sodium phosphate versus placebo (phase 3 trial)

To read more about “Ataxia-telangiectasia”

Lancet Neurol. 2024 Sep;23(9):871-882

Hemophilia B: Superiority of gene therapy with fidanacogene elaparvovec compared to prophylaxis to reduce bleeding and stabilize factor IX expression (phase 3 trial)

To read more about “Hemophilia B”

N Engl J Med. 2024 Sep 26;391(12):1108-1118

Hereditary hemorrhagic telangiectasia: Significant reduction in epitaxis severity with well-tolerated pomalidomide compared to placebo (phase 2 trial)

To read more about “Hereditary hemorrhagic telangiectasia”

N Engl J Med. 2024 Sep 19;391(11):1015-1027

B-cell chronic lymphocytic leukemia: Mutational profile in previously treated patients on acalabrutinib or ibrutinib (phase 3 trial)

To read more about “B-cell chronic lymphocytic leukemia”

Blood. 2024 Sep 5;144(10):1061-1068

Chronic myeloid leukemia: Major molecular response and favorable safety profile of asciminib compared to other tyrosine kinase inhibitors in newly diagnosed patients (phase 3 trial)

To read more about “Chronic myeloid leukemia”

N Engl J Med. 2024 Sep 12;391(10):885-898

Gastrointestinal stromal tumor: Rapid progression, faster resistance to treatment and shorter overall survival with imatinib interruption in non-progressing patients compared with treatment continuation (phase 3 trial)

To read more about “Gastrointestinal stromal tumor”

Lancet Oncol. 2024 Sep;25(9):1163-1175

Head and neck squamous cell carcinoma: Overall superiority for survival of finotonlimab addition to C5F chemotherapy with acceptable safety profile among recurrent/metastatic cancer (phase 3 trial)

To read more about “Squamous cell carcinoma of the hypopharynx”
To read more about “Squamous cell carcinoma of the larynx”
To read more about “Squamous cell carcinoma of the oral cavity”
To read more about “Squamous cell carcinoma of the oropharynx”

Nat Med. 2024 Sep;30(9):2568-2575

Leiomyosarcoma: Improvement of overall and progression-free survival with combined doxorubicin/trabectedin therapy, followed by trabectedin maintenance, as compared with doxorubicin alone, among patients with advanced disease (phase 3 trial)

To read more about “Leiomyosarcoma”

N Engl J Med. 2024 Sep 5;391(9):789-799

AA amyloidosis: Reduction of systemic inflammation and prevention of disease progression to end-stage renal disease by biological disease-modifying antirheumatic drugs (retrospective study)

To read more about “AA amyloidosis”

Ann Rheum Dis. 2024 Aug 27;83(9):1200-1207

Fanconi anemia: Excellent survival after allogeneic hematopoietic stem cell transplantation in children, with optimized conditioning treatment to avoid graft-versus-host disease (retrospective cohort study)

To read more about “Fanconi anemia”

Blood. 2024 Sep 19;144(12):1329-1342

Proteasome-associated autoinflammatory syndrome: Disease flares and rebound inflammation with baricitinib dose reductions necessitates development of flares criteria (retrospective study)

To read more about “Proteasome-associated autoinflammatory syndrome”

Ann Rheum Dis. 2024 Aug 27;83(9):1181-1188

Proximal spinal muscular atrophy: Favorable motor outcomes with preserved respiratory and feeding functions in treatment-naive infants treated by onasemnogene abeparvovec gene transfer therapy (prospective cohort study)

To read more about “Proximal spinal muscular atrophy”

Orphanet J Rare Dis. 2024 Sep 13;19(1):344

Therapeutic Approaches

Congenital generalized lipodystrophy: Recover metabolic health in generalised lipodystrophy mouse model by adipose tissue-selective AAV-mediated gene therapy

To read more about “Congenital generalized lipodystrophy”

Gene Ther. 2024 Sep;31(9-10):445-454

Congenital myasthenic syndrome: Restoration of neuromuscular function by an agonist antibody for human MuSK (ARGX-119) in a mouse model

To read more about “Congenital myasthenic syndrome”

Sci Transl Med. 2024 Sep 18;16(765):eado7189

Cystic fibrosis: Better CFTR modulator response among missense variants with the lowest CTFR residual activity on patient‑derived rectal organoids

To read more about “Cystic fibrosis”

Orphanet J Rare Dis. 2024 Sep 13;19(1):343

Cystic fibrosis: Combination of systemic and airway application may be the preferred route of AAV vector-mediated gene therapy delivery in ferret model

To read more about “Cystic fibrosis”

Gene Ther. 2024 Sep;31(9-10):499-510

Familial long QT syndrome: Normalization of pathologically-prolonged clinical QT index and cellular ventricular action potential duration using a novel KCNQ1 suppression-replacement gene therapy in rabbit model

To read more about “Familial long QT syndrome”

Eur Heart J. 2024 Sep 29;45(36):3751-3763

Gaucher disease: Greatest benefit in neuronopathic mouse model by improving AAV vector-mediated gene therapy with a designed thermostable form of glucocerebrosidase or with a neuronal-selective promoter

Read more (GCase thermostable form)
Read more (neuronal-selective promoter)

To read more about “Gaucher disease”

Gene Ther. 2024 Sep;31(9-10):439-444
Hum Mol Genet. 2024 Aug 18;33(17):1467-1480

Hirschsprung disease: Ability of enteric nervous system progenitors to differentiate into enteric neurons in vitro and mediate increased functional responses following transplantation into explants of patient-derived tissue

To read more about “Hirschsprung disease”

Gut. 2024 Aug 8;73(9):1441-1453

Neurofibromatosis type 1: Methodology and in-depth characterization of an ex vivo patient-derived explant model for disease-related cutaneous neuroﬁbromas

To read more about “Neurofibromatosis type 1”

J Invest Dermatol. 2024 Sep;144(9):2052-2065.e8

Osteogenesis imperfecta: Osseointegration enhacement of dental and orthopaedic implants by sclerostin antibody in a mouse model

To read more about “Osteogenesis imperfecta”

Bone. 2024 Sep:186:117167

Polyglutamine neurodegenerative diseases: Restoration of DNA repair enzymatic activity in vitro and amelioration of neurodegenerative symptoms in vivo by fructose-2,6-bisphosphate

To read more about “Huntington disease”
To read more about “Spinocerebellar ataxia type 3”

Proc Natl Acad Sci U S A. 2024 Sep 24;121(39):e2406308121

SORD deficiency: Phenotypic characterization of a Sord knockout rat model with a motor-predominant neuropathy closely similar to the human phenotype

To read more about “Autosomal dominant Charcot-Marie-Tooth disease type 2”
To read more about “Distal hereditary motor neuropathy”

Brain. 2024 Sep 3;147(9):3131-3143

Systemic sclerosis: Amelioration of experimental dermal and pulmonary fibrosis by an anti-IL1RAP antibody in mouse models

To read more about “Systemic sclerosis”

Ann Rheum Dis . 2024 Aug 27;83(9):1156-1168

X-linked erythropoietic protoporphyria/sideroblastic anemia: Knockin mouse models generation using CRISPR-CAS9 gene editing technology and their conditional synthetic lethal dependency on pyridoxine

To read more about “X-linked erythropoietic protoporphyria”
To read more about “X-linked sideroblastic anemia”

Blood. 2024 Sep 26;144(13):1418-1432

Biomarkers

Adrenocortical carcinoma: Expression and Prognostic Relevance of checkpoint molecules programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) in advanced patients

To read more about “Adrenocortical carcinoma”

J Clin Endocrinol Metab. 2024 Aug 13;109(9):2325-2334

Idiopathic intracranial hypertension: Sphingolipid in serum (S1P) and a phospholipid in CSF (LysoPC-16) as potential prognostic markers associated with subsequent optic nerve atrophy in new-onset patients

To read more about “Idiopathic intracranial hypertension”

Ann Neurol. 2024 Sep;96(3):595-607

Improvement of risk prediction for common and rare diseases based on plasma proteomic signatures

Nat Med. 2024 Sep;30(9):2489-2498

Lysosomal disease: Summary of both available and future biomarkers for gene therapy clinical trials

To read more about “Lysosomal disease”

Mol Ther. 2024 Sep 4;32(9):2930-2938

Sarcoidosis: Recruitment of CXCR4+type 1 innate lymphoid cells and associated molecular signature as biomarkers to distinguish from other skin granulomatous diseases

To read more about “Sarcoidosis”

J Clin Invest. 2024 Sep 3;134(17):e178711

Systemic sclerosis: Identification and validation of several biomarkers for disease trajectory

Read more (CCL24 marker)
Read more (PRMT5 marker)

To read more about “Systemic sclerosis”

Arthritis Care Res (Hoboken). 2024 Sep;76(9):1269-1277
Ann Rheum Dis. 2024 Aug 27;83(9):1144-1155

Diagnostic Approaches

Acute promyelocytic leukemia/Chronic myeloid leukemia: CRISPR-based RNA-fusion transcript detection assays for the diagnosis of fusion-driven leukemias

To read more about “Acute promyelocytic leukemia”
To read more about “Chronic myeloid leukemia”

Blood. 2024 Sep 19;144(12):1290-1299

Inflammatory syndromes: Circulating cell-free RNA in plasma as an analyte for differential diagnosis and quantification of specific tissues/organs injury in pediatric patients

To read more about “Kawasaki disease”
To read more about “Multisystem inflammatory syndrome in children and adults”

Proc Natl Acad Sci U S A. 2024 Sep 10;121(37):e2403897121

Systemic mastocytosis: Development of a promising OSTEO-score to predict diagnosis before bone marrow assessment in patients with unexplained osteoporosis

To read more about “Systemic mastocytosis”

Bone. 2024 Sep:186:117141

Neonatal Screening

Feasibility and acceptability of targeted sequencing at birth as a first-tier NBS approach to detect early-onset and/or treatable serious genetic conditions

Children (Basel). 2024 Jul 30;11(8):926

Feasibility of long-term follow-up surveillance thanks to standard quality measures collected by state public health programs, applicable across NBS conditions

J Public Health Manag Pract. 2024 Sep 6

Recessive monogenic lysosomal storage diseases and others: Relevance of biochemical assay as a second-tier method for NBS to filter pathogenic variants of unknown significance after first-tier NGS

To read more about “Metachromatic leukodystrophy”
To read more about “Krabbe disease”
To read more about “Mucopolysaccharidosis type 1”
To read more about “Glycogen storage disease due to acid maltase deficiency”
To read more about “Cerebrotendinous xanthomatosis”

Genet Med Open. 2023;1(1):100821

Patient Management and Therapy

Amyloid neuropathies: Comprehensive review from pathophysiology to disease treatment

To read more about “AL amyloidosis”
To read more about “Hereditary ATTR amyloidosis”

Ann Neurol. 2024 Sep;96(3):423-440

Brain tumors: Opportunities and regulatory challenges for implementing targeted radionuclide therapies into neuro-oncological practice based on the theranostic concept

To read more about “Glial tumor”
To read more about “Primary central nervous system lymphoma”
To read more about “Primary germ cell tumor of central nervous system”
To read more about “Tumor of meninges”

Lancet Oncol. 2024 Sep;25(9):e441-e451

Chronic graft versus host disease: Comprehensive overview of unmet needs and perspectives for improving prophylaxis and treatment

To read more about “Chronic graft versus host disease”

Blood. 2024 Sep 26;144(13):1363-1373

Fuchs endothelial corneal dystrophy: Use of single-cell RNA sequencing to improve clinical diagnostics, elucidate novel mechanisms and develop new treatments

To read more about “Fuchs endothelial corneal dystrophy”

Prog Retin Eye Res. 2024 Sep:102:101286

Immune-mediated neurological diseases: State of the art and future directions of CAR-T use

To read more about “Autoimmune encephalitis”
To read more about “Chronic inflammatory demyelinating polyneuropathy”
To read more about “Classic stiff person syndrome”
To read more about “Myasthenia gravis”
To read more about “Neuromyelitis optica spectrum disorder”

Ann Neurol. 2024 Sep;96(3):441-452

Neuroleptic malignant syndrome: Contemporary disease management focused on treatment in critical care settings

To read more about “Neuroleptic malignant syndrome”

N Engl J Med. 2024 Sep 26;391(12):1130-1138

Primary angiitis of the central nervous system: Overwiew of all disease aspects in adults

To read more about “Primary angiitis of the central nervous system”

N Engl J Med. 2024 Sep 19;391(11):1028-1037

Primary biliary cholangitis: Recent progress on epidemiology, pathogenesis, diagnosis and management

To read more about “Primary biliary cholangitis”

Lancet. 2024 Sep 14;404(10457):1053-1066

Pseudoxanthoma elasticum: Genetics, pathophysiology, multi-systemic manifestations, previous and future clinical trials of causative treatments

To read more about “Pseudoxanthoma elasticum”

Prog Retin Eye Res. 2024 Sep:102:101274

Rare disorder of the anterior segment of the eye: Genotype-phenotype correlations, current and emerging mechanisms to develop new treatments

To read more about “Rare disorder of the anterior segment of the eye”

Prog Retin Eye Res. 2024 Sep:102:101288

Recessive dystrophic epidermolysis bullosa: Narrative review of systemic features and promising research avenues

To read more about “Autosomal recessive generalized dystrophic epidermolysis bullosa, intermediate form”
To read more about “Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form”
To read more about “Recessive dystrophic epidermolysis bullosa inversa”

J Invest Dermatol. 2024 Sep;144(9):1943-1953

Thrombotic thrombocytopenic purpura: Awareness and progress in diagnosis and management over the past 100 years

To read more about “Thrombotic thrombocytopenic purpura”

Blood. 2024 Sep 12;144(11):1143-1152

Tumor of hematopoietic and lymphoid tissues: Current developments of T cell-redirecting therapies and novel targeting strategies for advancing immunotherapeutic targets

To read more about “Tumor of hematopoietic and lymphoid tissues”

Mol Ther. 2024 Sep 4;32(9):2856-2891

Recommendations

Achondroplasia: International expert opinion on the combined use of vosoritide and limb surgery in children and adolescents

To read more about “Achondroplasia”

Orphanet J Rare Dis. 2024 Sep 17;19(1):347

Rare disease with thoracic aortic aneurysm and aortic dissection: Clinical practice guidelines on diagnosis, surveillance and treatment

To read more about “Rare disease with thoracic aortic aneurysm and aortic dissection”

Eur Heart J. 2024 Sep 29;45(36):3538-3700

Epidemiology

Neurofibromatosis/schwannomatosis: An updated genetic and epidemiological study following new published diagnostic criteria for NF2-related disease in UK

To read more about “Neurofibromatosis/schwannomatosis”

J Med Genet. 2024 Aug 29;61(9):856-860

Systemic sclerosis: Demographic and clinical data of patients in a Latvian cohort

To read more about “Systemic sclerosis”

Orphanet J Rare Dis. 2024 Sep 30;19(1):361

Trisomy 13 syndrome: Investigation of survival changes in Japenese patients based on prognostic and management evolutions

To read more about “Trisomy 13 syndrome”

Am J Med Genet A. 2024 Sep;194(9):e63710

Wilson disease: Real-world data on prevalence and patient characteristics in Germany

To read more about “Wilson disease”

Orphanet J Rare Dis. 2024 Sep 11;19(1):335

Functional Impact

Classic galactosemia: Exploration of social cognition, psychosocial development and well-being in patients

To read more about “Classic galactosemia”

Orphanet J Rare Dis. 2024 Sep 6;19(1):325

Glycogen storage disease due to acid maltase deficiency (Pompe disease): Qualitative insights into the perceptions and experiences of pediatric patients and their caregivers

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

Orphanet J Rare Dis. 2024 Sep 28;19(1):358

Inherited epidermolysis bullosa: Economic burden and patients' health-related quality of life in Spain

To read more about “Inherited epidermolysis bullosa”

Orphanet J Rare Dis. 2024 Sep 23;19(1):352

Rare genetic intellectual disability: Protocol presentation to develop a generic core patient-reported outcome set for children and adults

To read more about “Rare genetic intellectual disability”

Orphanet J Rare Dis. 2024 Sep 27;19(1):354

Summary of the edition of 19 December 2024

Editorial
Political news
Scientific news
And also...