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Edition of 16 October 2023

New Syndromes

BMP2 mutations result in a skeletal dysplasia spectrum

A new study published in Genetics in Medicine highlight phenotypes of patients harboring monoallelic missense variants in BMP2, and expand the phenotypic spectrum known to be linked with BMP2 variants (a gene coding for bone morphogenic proteins), namely multiple congenital anomaly syndrome through a haploinsufficiency mechanism. Retrospective chart review of 18 individuals was compared to published cases, and zebrafish model was built. The study shows some variants promote embryonic ventralization and, beyond the usual cases, identified patients with neural tube defects, structural brain anomalies, and endocrinopathies. This expansion of reported phenotypes suggests multidisciplinary medical monitoring, and management of patients with BMP2-related skeletal dysplasia spectrum.

To read more about “Primary bone dysplasia”

Genet Med . 2023 Aug;25(8):100863

Inactivation of DRG1, encoding a translation factor GTPase, causes a recessive neurodevelopmental disorder

A new study published in Genetics in Medicine identified inherited recessive variants in the gene coding for DRG1 (a GTPases implicated in translation), within 4 individuals (from 3 unrelated families) who express neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature, and craniofacial anomalies. Various analyses show a (of which mouse model) defines a new Mendelian disorder of DRG1 deficiency. The study highlights DRG1's importance for normal mammalian development and underscores the significance of translation factor GTPases in human physiology and homeostasis.

Genet Med . 2023 Sep;25(9):100893

ERI1 mutations cause a recessive phenotypic dichotomy

A new study published in the American Journal of Human Genetics identified bi-allelic ERI1 variants in 8 individuals (from 7 unrelated families) who express a phenotypic dichotomy (5 with a severe spondyloepimetaphyseal dysplasia, 3 with mild intellectual disability and digital anomalies). Various analyses (whom iPSCs ) establishe an entity previously unreported in OMIM and provides a model showing a more severe effect of missense alleles than null alleles within recessive genotypes, suggesting a key role of ERI1-mediated RNA metabolism in human skeletal patterning and chondrogenesis.

Am J Hum Genet . 2023 Jul 6;110(7):1068-1085

P4HTM mutations cause a novel form of syndromic obesity

A new study published in Diabetes identified five seven biallelic variants in P4HTM (a gene implied in transmembrane hydroxylase), with a de novo monogenetic recessive one, within children (partly among five consanguineous families) who express severe obesity. Most carriers also present with hypotonia, cognitive impairment, and/or developmental delay, and some died from pneumonia. Numerical model suggest that these mutations destabilized the active conformation of the substrate binding domain. P4HTM deficiency is a novel form of syndromic obesity, affecting 1.5% of our children with obesity associated with high mortality.

To read more about “Syndromic obesity”

Diabetes . 2023 Sep 1;72(9):1228-1234

New Genes

CMT2 (Autosomal dominant Charcot-Marie-Tooth disease type 2) : Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies the disease

To read more about “Autosomal dominant Charcot-Marie-Tooth disease type 2”

Am J Hum Genet . 2023 Aug 3;110(8):1394-1413

Biallelic variants in CRIPT cause a Rothmund-Thomson-like syndrome with increased cellular senescence

To read more about “Rothmund-Thomson syndrome”

Genet Med . 2023 Jul;25(7):100836

LHX2 haploinsufficiency causes a variable neurodevelopmental disorder

To read more about “on-specific syndromic intellectual disability”

Genet Med . 2023 Jul;25(7):100839

ALS (Amyotrophic lateral sclerosis) : CGG repeat expansion in LRP12

To read more about “Amyotrophic lateral sclerosis”

Am J Hum Genet . 2023 Jul 6;110(7):1086-1097

Autosomal SLE (systemic lupus erythematosus) : Association with a loss-of-function mutation in TRPC6

To read more about “Autosomal systemic lupus erythematosus”

Ann Rheum Dis . 2023 Aug;82(8):1120-1122

Clinical Research

Sickle cell disease : Relationship between hemoglobin, hemolysis, and transcranial Doppler velocities in children, a Results from a long-term natural history study in Italy in the era of multimodal therapy

To read more about “Sickle cell disease and related diseases”

Bone . 2023 Sep:174:116819

ALL (Acute lymphoblastic leukemia) : Poverty and relapse risk in children, a Children's Oncology Group study AALL03N1 report

To read more about “Acute lymphoblastic leukemia”

Blood . 2023 Jul 20;142(3):221-229

BBS (Bardet-Biedl syndrome) : Burden of hyperphagia and obesity, a multicountry survey

To read more about “Bardet-Biedl syndrome”

Orphanet J Rare Dis . 2023 Jul 7;18(1):182

Achondroplasia : Higher rates of non-skeletal complications and greater healthcare needs, compared to the general UK population, a matched cohort study using the CPRD database

To read more about “Achondroplasia”

BMC Public Health . 2022 Mar 17;22(1):521

Giant cell arteritis : Burden, Causes, and Outcomes of Hospitalization, a US National Cohort Study

To read more about “Giant cell arteritis”

Arthritis Care Res (Hoboken) . 2023 Aug;75(8):1830-1837

SAPHO syndrome : Sexual function assessment, a cross-sectional study

To read more about “SAPHO syndrome”

Orphanet J Rare Dis . 2023 Jul 27;18(1):217

Erdheim-Chester disease : Prevalence, patterns and outcomes of cardiac involvement

To read more about “Erdheim-Chester disease”

Arthritis Care Res (Hoboken) . 2023 Aug;75(8):1698-1705

Infantile hemangioma : Long-term follow-up of patients with extensive segmental infantile hemangioma of the cervical or facial region, a French single-center prospective study

Arch Pediatr . 2023 Aug;30(6):366-371

HPP (Hypophosphatasia) : Zinc and vitamin D deficiency and supplementation, a retrospective study

To read more about “Hypophosphatasia”

Bone . 2023 Oct:175:116849

Diffuse cutaneous systemic sclerosis : Phase 3, Lenabasum (a Cannabinoid Type 2 Receptor Agonist), Efficacy and Safety from a randomized trial

To read more about “Diffuse cutaneous systemic sclerosis”

Arthritis Rheumatol . 2023 Sep;75(9):1608-1618

Diffuse Cutaneous Systemic Sclerosis, in early phase : Phase IIa, Ziritaxestat, a 24-Weeks Randomized, Double-Blind, Placebo-Controlled Study

To read more about “Diffuse cutaneous systemic sclerosis”

Arthritis Rheumatol . 2023 Aug;75(8):1434-1444

PHN (Paroxysmal nocturnal hemoglobinuria) : Phase I/II, Crovalimab, Long-term results from the COMPOSER trial

To read more about “Paroxysmal nocturnal hemoglobinuria”

Eur J Haematol . 2023 Aug;111(2):300-310

Systemic sclerosis : Reporting and Representativeness of Race, Ethnicity, and Socioeconomic Status, a Randomized Trials and Observational Study

To read more about “Systemic sclerosis”

Arthritis Care Res (Hoboken) . 2023 Aug;75(8):1698-1705

Cleft palate : Timing of Primary Surgery

To read more about “Cleft palate”

N Engl J Med . 2023 Aug 31;389(9):795-807

GH Deficiency : Long-term Pegylated GH for Children, a Large, Prospective, Real-world Study

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

J Clin Endocrinol Metab . 2023 Jul 14;108(8):2078-2086

Papillary Craniopharyngiomas : BRAF-MEK Inhibition for new diagnosis

To read more about “Craniopharyngioma”

N Engl J Med . 2023 Jul 13;389(2):118-126

SMA (Proximal spinal muscular atrophy) : Long-term nusinersen treatment across a wide spectrum of severity, a real-world experience

To read more about “Proximal spinal muscular atrophy”

Orphanet J Rare Dis . 2023 Aug 4;18(1):230

ALL (Acute lymphoblastic leukemia) : Blinatumomab Added to Chemotherapy, for children

To read more about “Acute lymphoblastic leukemia”

N Engl J Med . 2023 Apr 27;388(17):1572-1581

Sickle cell disease : Treatment of vaso-occlusive crisis, implementation and evaluation of a multimodal pain protocol

To read more about “Sickle cell disease and related diseases”

Eur J Haematol . 2023 Sep;111(3):382-390

ASPS (Alveolar soft tissue sarcoma) : Atezolizumab

To read more about “Alveolar soft tissue sarcoma”

N Engl J Med . 2023 Sep 7;389(10):911-921

Congenital IGHD : Weekly Somapacitan in GH Deficiency, Efficacy, Safety, a 4-Year Treatment/Disease Burden Results From REAL 3

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

J Clin Endocrinol Metab . 2023 Sep 18;108(10):2569-2578

Fibrous dysplasia of bone, refractory to bisphosphonate : Denosumab, a retrospective multicentric study

To read more about “Fibrous dysplasia of bone”

Bone . 2023 Sep:174:116819

Infantile hypophosphatasia : Effects of asfotase alfa in adults with pediatric-onset over 24 months of treatment

To read more about “Infantile hypophosphatasia”

Bone . 2023 Oct:175:116856

Juvenile idiopathic arthritis : Baricitinib, a monocentric case series

To read more about “Juvenile idiopathic arthritis”

Ann Rheum Dis . 2023 Jul;82(7):994-995

FD (Fabry disease) : Safety and tolerability of agalsidase beta infusions shorter than 90 min, evidence from a Japanese post-marketing study

To read more about “Fabry disease”

phanet J Rare Dis . 2023 Jul 24;18(1):209

Therapeutic Approaches

ALS (Amyotrophic lateral sclerosis) : Novel rAAV vector mediated intrathecal HGF delivery has an impact on neuroimmune modulation in the ALS motor cortex with TDP-43 pathology

To read more about “Amyotrophic lateral sclerosis”

Gene Ther . 2023 Aug;30(7-8):560-574

Retinitis pigmentosa : Gene augmentation for autosomal dominant retinitis pigmentosa using rhodopsin genomic loci nanoparticles in the P23H+/− knock-in murine model

To read more about “Retinitis pigmentosa”

Gene Ther . 2023 Aug;30(7-8):628-640

FA (Friedreich ataxia) : Continuous, but not intermittent, regimens of hypoxia prevent and reverse ataxia in a murine model

To read more about “Friedreich ataxia”

Hum Mol Genet . 2023 Aug 7;32(16):2600-2610

Neurofibromatosis type 1, related cutaneous : Existing and Developing Preclinical Models

To read more about “Neurofibromatosis type 1”

J Invest Dermatol . 2023 Aug;143(8):1378-1387

Biomarkers

AIH (Autoimmune hepatitis) : Noninvasive biomarkers for the diagnosis and management

To read more about “Autoimmune hepatitis”

Hepatology . 2022 Dec;76(6):1862-1879

Diastrophic dysplasia : Identification of potential non-invasive biomarkers

To read more about “Diastrophic dysplasia”

Bone . 2023 Oct:175:116838

Diagnostic Approaches

Neurofibromatosis type 1: Preimplantation genetic testing, more than 20 years of clinical experience

To read more about “Neurofibromatosis type 1”

Eur J Hum Genet . 2023 Aug;31(8):918-924

Lysosomal disease : Screening in a selected pediatric population, the case of Gaucher disease and acid sphingomyelinase deficiency

To read more about “Lysosomal disease”

Orphanet J Rare Dis . 2023 Jul 21;18(1):197

FPLD (Familial partial lipodystrophy) : Pelvis Magnetic Resonance Imaging to Diagnose

To read more about “Familial partial lipodystrophy”

J Clin Endocrinol Metab . 2023 Jul 14;108(8):e512-e520

Multi-omics for better and faster rare disease diagnosis

Nat Med . 2023 Jul;29(7):1615-1616

Neonatal screening

Actionability of unanticipated monogenic disease risks in newborn genomic screening: Findings from the BabySeq Project

Am J Hum Genet . 2023 Jul 6;110(7):1034-1045

Patient Management and Therapy

Aplastic anemia : Research progress on the hematopoietic microenvironment

To read more about “Rare aplastic anemia”

Eur J Haematol . 2023 Aug;111(2):172-180

Rett syndrome : Blarcamesine, leveraging knowledge from small trials for rare disease drug adevelopment

To read more about “Rett syndrome”

Br J Clin Pharmacol . 2023 Jul 10. doi: 10.1111/bcp.15843

SLE (Systemic lupus erythematosus) : Risks, mechanisms and therapeutic targets, the pathogenesis

To read more about “Systemic lupus erythematosus”

Ann Rheum Dis . 2023 Aug;82(8):999-1014

Imerslund-Gräsbeck syndrome : a comprehensive review of reported cases

To read more about “Imerslund-Gräsbeck syndrome”

Orphanet J Rare Dis . 2023 Sep 14;18(1):291

Recommendations

EBS (Epidermolysis bullosa simplex) : Consensus-based guidelines for the provision of palliative and end-of-life care

To read more about “Epidermolysis bullosa simplex”

Orphanet J Rare Dis . 2023 Sep 4;18(1):268

Monosomy 22q13.3 (Monosomy 22q13.3) : Updated consensus guidelines on the management

To read more about “Monosomy 22q13.3”

Am J Med Genet A . 2023 Aug;191(8):2015-2044

CML (Chronic myeloid leukemia) : Cardiovascular risk, a multidisciplinary consensus on screening and management

To read more about “Chronic myeloid leukemia”

Eur J Haematol . 2023 Aug;111(2):201-210

Epidemiology

Epidemiological research on rare diseases using large-scale online search queries and reported case data

Orphanet J Rare Dis . 2023 Aug 9;18(1):236

KBG syndrome : Prenatal and neonatal outcomes, documentation and prevalence in a cohort

To read more about “KBG syndrome”

m J Med Genet A . 2023 Sep;191(9):2364-2375

Congenital hypopituitarism : Diagnosis and Incidence in Denmark, a National Observational Study

To read more about “Non-acquired combined pituitary hormone deficiency”

J Clin Endocrinol Metab . 2023 Sep 18;108(10):2475-2485

Quality of Life

PKAN (Pantothenate kinase-associated neurodegeneration) : Patient and caregiver experiences, results from a patient community survey

To read more about “Pantothenate kinase-associated neurodegeneration”

Orphanet J Rare Dis . 2023 Aug 31;18(1):257

CCLA (Noonan syndrome) : The most important problems and needs of rasopathy patients

To read more about “Noonan syndrome”

Orphanet J Rare Dis . 2023 Jul 21;18(1):198

Hemophilia A : The impact of bleeding event frequency on health-related quality of life and work productivity outcomes in a European cohort of adults, insights from the CHESS II study

To read more about “Hemophilia A”

Orphanet J Rare Dis . 2023 Aug 3;18(1):227

SLE (Systemic lupus erythematosus) : Health-Related Quality of Life in Adults With Adolescent- and Adult-Onset, A Longitudinal Study of a Multiethnic US Cohort

To read more about “Systemic lupus erythematosus”

Arthritis Care Res (Hoboken) . 2023 Jul;75(7):1416-142

Summary of the edition of 16 October 2023

Editorial
Political news
Scientific news
And also...