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.
- 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.
- 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.
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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%
- 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%
- 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
- 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
- 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.
- 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%
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Eur J Med Genet. 2019 Aug;62(8):103663
Unique bioinformatic approach and comprehensive reanalysis improve diagnostic yield of clinical exomes
- 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
- 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
- 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
- To read more about “Primary ciliary dyskinesia”
- Translational Science of Rare Diseases 4 (2019) 51–75
Polycythemia vera: How I treat polycythemia vera
- To read more about “Polycythemia vera”
- Blood. 2019 Jul 25;134(4):341-352
Incontinentia pigmenti: A review of incontinentia pigmenti in adults
- 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
- To read more about “Marfan syndrome”
- Genet Med. 2019 Aug;21(8):1683-1690
Pheochromocytoma and paraganglioma : A review
- 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
- Ann Neurol. 2019 Sep;86(3):332-343
Recommendations
Primary sclerosing cholangitis: British Society of Gastroenterology guidelines for the diagnosis and management
- To read more about “Primary sclerosing cholangitis”
- Gut. 2019 Sep;68(9):1545-1575
Juvenile localised scleroderma: Consensus-based recommendations for the management
- To read more about “Localized scleroderma”
- Ann Rheum Dis. 2019 Aug;78(8):1019-1024
Costello syndrome: Clinical phenotype, genotype, and management guidelines
- 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
- 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
- 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
- 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
- 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
- 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
- To read more about “Caudal regression sequence”
- Am J Med Genet A. 2019 Sep;179(9):1799-1814
