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Edition of 02 October 2019

New Syndromes

De novo variants in WDR37 are associated with epilepsy, colobomas, dysmorphism, developmental delay, intellectual disability, and cerebellar hypoplasia

A recent study published in the American Journal of Human Genetics identified five peadiatrics patients with de novo variants in WDR37, which encodes a member of the WD40 repeat protein family. The patient exhibited shared phenotypes of epilepsy, colobomas, facial dysmorphology reminiscent of CHARGE syndrome, developmental delay and intellectual disability, and cerebellar hypoplasia. This study suggested that variants in WDR37 underlied a novel syndromic neurological disorder.

Consult the pubmed abstract

Am J Hum Genet. 2019 Aug 1;105(2):413-424

De novo missense variants in WDR37 cause a severe multisystemic syndrome

A new article published in the American Journal of Human Genetics reported four de novo missense variants predicted to affect the N-terminal region of WDR37-p.Ser119Phe, p.Thr125Ile, p.Ser129Cys, and p.Thr130Ile-in unrelated individuals with a previously unrecognized syndrome.

Features of WDR37 syndrome include the following: ocular anomalies such as corneal opacity, Peters anomaly, coloboma, and microcornea, dysmorphic facial features, significant neurological impairment with structural brain defects and seizures, poor feeding, poor post-natal growth, variable skeletal, cardiac, and genitourinary defects, and death in infancy in one individual. WDR37 encodes a protein of unknown function with seven predicted WD40 domains. This study identified variants in WDR37 associated with human disease and provided insight into its essential role in vertebrate development and possible molecular functions.

Consult the pubmed abstract

Am J Hum Genet. 2019 Aug 1;105(2):425-433

De novo variants disturbing the transactivation capacity of POU3F3 cause a characteristic neurodevelopmental disorder

A new study recently published in the American Journal of Human Genetics identified 19 individuals with with heterozygous POU3F3 disruptions, most of which are de novo variants. All individuals had developmental delays and/or intellectual disability and impairments in speech and language skills. Thirteen individuals had characteristic low-set, prominent, and/or cupped ears. Brain abnormalities were observed in seven of eleven MRI reports.

The identification and functional cell-based analyses of pathogenic variants in POU3F3, coupled with a clinical characterization, implicated disruptions of this gene in a characteristic neurodevelopmental disorder.

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Am J Hum Genet. 2019 Aug 1;105(2):403-412

Biallelic variant in AGTPBP1 causes infantile lower motor neuron degeneration and cerebellar atrophy

A new study published in the American Journal of Medical Genetics identified two individuals with childhood-onset neurodegeneration with cerebellar atrophy in whom a biallelic missense AGTPBP1 variant (NM_001330701.1:c.2396G>T, p.Arg799Leu) was identified by whole exome sequencing. Affected individuals in this report corresponded to the severe infantile spectrum of the disease and underlined the severe pathogenic effect of this missense variant.

Consult the pubmed abstract

Am J Med Genet A. 2019 Aug;179(8):1580-1584

New Genes

Brittle Hair phenotype is caused by bi-allelic TARS mutations

To read more about “Trichothiodystrophy”

Am J Hum Genet. 2019 Aug 1;105(2):434-440

Microcephalic primordial dwarfism is caused by biallelic variants in DNA2

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To read more about “Microcephalic primordial dwarfism”

Hum Mutat. 2019 Aug;40(8):1063-107

Cerebellar degeneration and motor neuropathy is caused by biallelic variants in AGTPBP1, involved in tubulin deglutamylation

Consult the pubmed abstract

To read more about “Pontocerebellar hypoplasia type 1”

Eur J Hum Genet. 2019 Sep;27(9):1419-1426

Muscle-specific cytochrome c oxidase deficiency is caused by COX6A2 variants

Consult the pubmed abstract

To read more about “Isolated cytochrome C oxidase deficiency”

Ann Neurol. 2019 Aug;86(2):193-202

A heterozygous, intragenic deletion of CNOT2 recapitulates the phenotype of 12q15 deletion syndrome

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To read more about “12q15q21.1 microdeletion syndrome”

Am J Med Genet A. 2019 Aug;179(8):1615-1621

Autism and developmental disability caused by KCNQ3 gain-of-function variants

Consult the pubmed abstract

Ann Neurol. 2019 Aug;86(2):181-192

Clinical Research

Muenke syndrome: A large cohort study evaluated medical and surgical comorbidities and long-term management

Consult the pubmed abstract

To read more about “Muenke syndrome”

Am J Med Genet A. 2019 Aug;179(8):1442-1450

Prader-Willi syndrome: A study showed that growth hormone therapy may influence intelligence impacted by Prader-Willi genetic subtypes

Consult the pubmed abstract

To read more about “Prader-Willi syndrome”

Am J Med Genet A. 2019 Sep;179(9):1826-1835

Beckwith-Wiedemann syndrome: A study evaluating phenotype evolution and health issues showed that adult health conditions are mostly consequent to pediatric issues, underlying the preventive role of follow-up strategies in childhood

Consult the pubmed abstract

To read more about “Beckwith-Wiedemann syndrome”

Am J Med Genet A. 2019 Sep;179(9):1691-1702

Systemic lupus erythematosus: A study showed that lower scores of SF-36 physical function independently predicted mortality

Consult the pubmed abstract

To read more about “Systemic lupus erythematosus”

https://www.ncbi.nlm.nih.gov/pubmed/30144293

Maternally-inherited spastic paraplegia: A United Kingdom-based mitochondrial disease cohort study showed that MT-ATP6-related mitochondrial DNA disease is best conceptualized as a mitochondrial disease spectrum disorder

Consult the pubmed abstract

To read more about “MT-ATP6-related mitochondrial spastic paraplegia”

Ann Neurol. 2019 Aug;86(2):310-315

Severe hemophilia A: A study analyzed the timing of inhibitor development in more than 1000 previously untreated patients

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To read more about “Hemophilia A”

Blood. 2019 Jul 18;134(3):317-320

Multiple myeloma: A phase 1b study of daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma demontrasted an overall response rate of 84%

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To read more about “Multiple myeloma”

Blood. 2019 Aug 1;134(5):421-431

Multiple myeloma: A phase 1b study of isatuximab plus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma demonstrated a potential meaningful clinical activity with an overall response rate of 62%

Consult the pubmed abstract

To read more about “Multiple myeloma”

Blood. 2019 Jul 11;134(2):123-133

Multiple myeloma: A European retrospective chart review showed that real-world data could be used to help develop strategies for improving survival

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To read more about “Multiple myeloma”

Eur J Haematol. 2019 Aug;103(2):107-115

Chronic lymphocytic leukemia: A randomized phase 3 study showed that overall survival and progression free survival were superior with ibrutinib plus rituximab compared to standard chemotherapy in previously untreated patients

Consult the pubmed abstract

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

N Engl J Med. 2019 Aug 1;381(5):432-443

Chronic lymphocytic leukemia: In a real-life cohort study with patient still on ibrutinib after at least three years of treatment, BTK and PLCG2 mutations were detected in 57% and 13% of the next-generation sequencing samples, respectively.

Consult the pubmed abstract

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

Blood. 2019 Aug 15;134(7):641-644

B-cell non-Hodgkin lymphoma: A study showed that CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma were associated with a 2-year progression-free survival of 30%

Consult the pubmed abstract

To read more about “B-cell non-Hodgkin lymphoma”

Blood. 2019 Aug 15;134(7):626-635

Follicular lymphoma: A study showed that CD19 CAR-T cell immunotherapy is highly effective in adults with clinically aggressive relapsed or refractory follicular lymphoma with durable remission in a high proportion of patients

Consult the abstract

To read more about “Follicular lymphoma”

Blood (2019): blood.2019000905. Web. 12 Sept2019.

Follicular lymphoma: A randomized phase 2 trial showed that short regimen of rituximab plus lenalidomide in untreated patients improved complete response rate and progression free survival compared to rituximab only

Consult the pubmed abstract

To read more about “Follicular lymphoma”

Blood. 2019 Jul 25;134(4):353-362

Hodgkin lymphoma: A phase 2 study showed that brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine for nonbulky stage I/II classical Hodgkin lymphoma without radiation produced a high complete response rate

Consult the pubmed abstract

To read more about “https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=3739”

Blood. 2019 Aug 15;134(7):606-613

Biomarkers

Moyamoya angiopathy: Predictors of clinical or cerebral lesion progression in adult

Consult the pubmed abstract

To read more about “Moyamoya angiopathy”

Neurology. 2019 Jul 23;93(4):e388-e397

Diffuse systemic sclerosis: A European Scleroderma Trials and Research (EUSTAR) analysis identified predictors of disease worsening defined by progression of organ damage

Consult the pubmed abstract

To read more about “Systemic sclerosis”

Ann Rheum Dis. 2019 Sep;78(9):1242-1248

Sporadic Creutzfeldt-Jakob disease: Cerebrospinal fluid and plasma tau levels were significantly associated with survival time

Consult the pubmed abstract

To read more about “Sporadic Creutzfeldt-Jakob disease”

JAMA Neurol. 2019 May 6

Therapeutic Approaches

Localized scleroderma: A study showed that bone morphogenetic protein-6 inhibited fibrogenesis offering treatment options for fibrotic skin disease

Consult the pubmed abstract

To read more about “Localized scleroderma”

J Invest Dermatol. 2019 Sep;139(9):1914-1924.e6

Recessive dystrophic epidermolysis bullosa: Efficient gene reframing therapy with CRISPR/Cas9 to a recurrent frameshift mutation in COL7A1

Consult the pubmed abstract

To read more about “Recessive dystrophic epidermolysis bullosa, generalized intermediate”

J Invest Dermatol. 2019 Aug;139(8):1711-1721

Chronic lymphocytic leukemia: A study showed that ROR1-targeted delivery of miR-29b induced cell cycle arrest and therapeutic benefit in vivo in a mouse model

Consult the pubmed abstract

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

Blood. 2019 Aug 1;134(5):432-444.

Chronic lymphocytic leukemia: A study showed that inhibition of IGF1R offered efficacious salvage treatment of PI3K-δ inhibitor-resistant tumors in a murine model

Consult the pubmed abstract

To read more about “B-cell non-Hodgkin lymphoma”

Blood. 2019 Aug 8;134(6):534-547

Primary cutaneous T-cell lymphoma: A study showed that combined inhibition of Bcl-2 and NFκB synergistically induced cell death

Consult the abstract

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

Blood 2019 134:445-455

Hepatocellular carcinoma: A study showed the clinical potential of combining sorafenib with GPC3-targeted CAR T cells in mouse models

Consult the pubmed abstract

To read more about “Hepatocellular carcinoma”

Mol Ther. 2019 Aug 7;27(8):1483-1494

Glioblastoma: A study showed that acquired temozolomide resistance in MGMT-deficient glioblastoma cells was associated with regulation of DNA repair by DHC2

Consult the pubmed abstract

To read more about “Glioblastoma”

Brain. 2019 Aug; 142(8): 2352–2366

Diagnostic Approaches

Systemic lupus erythematosus: A study showed that the presence of anti-NR2 antibodies in patients with systemic lupus erythematosus with fatigue was a helpful diagnostic tool

Consult the pubmed abstract

To read more about “Systemic lupus erythematosus”

Ann Rheum Dis. 2019 Sep;78(9):1226-1234

Cholangiocarcinoma: Specific changes in serum concentrations of certain metabolites are useful to differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma and primary sclerosing cholangitis

Consult the pubmed abstract

To read more about “Cholangiocarcinoma”
To read more about “Hepatocellular carcinoma”
To read more about “Primary sclerosing cholangitis”

Hepatology. 2019 Aug;70(2):547-562

Update on the use of exome sequencing in the diagnosis of fetal abnormalities

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Eur J Med Genet. 2019 Aug;62(8):103663

Unique bioinformatic approach and comprehensive reanalysis improve diagnostic yield of clinical exomes

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Eur J Hum Genet. 2019 Sep;27(9):1398-1405

An algorithm as a diagnostic tool for central ocular motor disorders, also to diagnose rare disorders

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Orphanet J Rare Dis. 2019 Aug 8;14(1):193

The demise of preimplantation genetic testing for aneuploidy in Hungary and its effect on patient care

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Eur J Med Genet. 2019 Aug;62(8):103669

Patient management and therapy

Primary ciliary dyskinesia: A review of a genetic disorder of motile cilia

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To read more about “Primary ciliary dyskinesia”

Translational Science of Rare Diseases 4 (2019) 51–75

Polycythemia vera: How I treat polycythemia vera

Consult the pubmed abstract

To read more about “Polycythemia vera”

Blood. 2019 Jul 25;134(4):341-352

Incontinentia pigmenti: A review of incontinentia pigmenti in adults

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To read more about “Incontinentia pigmenti”

Am J Med Genet A. 2019 Aug;179(8):1415-1419

Marfan syndrome: Improved clinical history results in expanded natural history

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To read more about “Marfan syndrome”

Genet Med. 2019 Aug;21(8):1683-1690

Pheochromocytoma and paraganglioma : A review

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To read more about “Sporadic pheochromocytoma/secreting paraganglioma”

N Engl J Med 2019; 381:552-565

Intellectual and developmental disabilities research centers: Fifty years of scientific accomplishments

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Ann Neurol. 2019 Sep;86(3):332-343

Recommendations

Primary sclerosing cholangitis: British Society of Gastroenterology guidelines for the diagnosis and management

Consult the pubmed abstract

To read more about “Primary sclerosing cholangitis”

Gut. 2019 Sep;68(9):1545-1575

Juvenile localised scleroderma: Consensus-based recommendations for the management

Consult the pubmed abstract

To read more about “Localized scleroderma”

Ann Rheum Dis. 2019 Aug;78(8):1019-1024

Costello syndrome: Clinical phenotype, genotype, and management guidelines

Consult the pubmed abstract

To read more about “Costello syndrome”

Am J Med Genet A. 2019 Sep;179(9):1725-1744

Giant cell arteritis: 2018 EULAR recommendations for a core data set to support observational research and clinical care

Consult the pubmed abstract

To read more about “Giant cell arteritis”

Ann Rheum Dis. 2019 Sep;78(9):1160-1166

Epidemiology

Isolated postaxial polydactyly: Epidemiologic characteristics from a multicenter birth defects study

Consult the pubmed abstract

To read more about “Postaxial polydactyly type A”
To read more about “Postaxial polydactyly type B”

Am J Med Genet A. 2019 Aug;179(8):1432-1441

Tuberculosis: Epidemiology of tuberculosis among children and adolescents in the USA, 2007-17: An analysis of national surveillance data

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To read more about “Tuberculosis”

Lancet Public Health. 2019 Aug 21

Myeloproliferative neoplasms: Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population

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To read more about “Myeloproliferative neoplasm”

Blood. 2019 Aug 1;134(5):469-479

Acute lymphoblastic leukaemia : A report on survival in adult from the Swedish ALL Registry

Consult the pubmed abstract

Eur J Haematol. 2019 Aug;103(2):88-98

Non-syndromic sacral agenesis: Descriptive and risk factor analysis from the National Birth Defects Prevention Study, 1997-2011

Consult the pubmed abstract

To read more about “Caudal regression sequence”

Am J Med Genet A. 2019 Sep;179(9):1799-1814

Summary of the edition of 02 October 2019

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