Absence of pathogenic mutations in CD59 in chronic inflammatory demyelinating polyradiculoneuropathy

ABSTRACTObjectiveMutations in CD59 cause CIDP-like polyneuropathy in children with inherited chronic hemolysis. We hypothesized that mutations in CD59 might be found in a subset of sporadic CIDP patients.Methods5 patients from two centers, fulfilling the EFNS/PNS diagnostic criteria for CIDP were included. CD59 coding region was amplified by PCR and Sanger sequenced.ResultsOne rare variant was detected in a patient which resulted in a synonymous change and predicted to be neutral. Pathogenic variants were absent in our cohort.InterpretationOur pilot study suggests that mutations in CD59 are absent in adult-onset sporadic CIDP.

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A multiplex PCR amplicon sequencing assay to screen genetic hearing loss variants in newborns

BMC Medical Genomics ◽

10.1186/s12920-021-00906-1 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Haiyan Yang ◽

Hongyu Luo ◽

Guiwei Zhang ◽

Junqing Zhang ◽

Zhiyu Peng ◽

...

Keyword(s):

Hearing Loss ◽

Pilot Study ◽

Multiplex Pcr ◽

Internal Consistency Reliability ◽

Amplicon Sequencing ◽

Coding Region ◽

Pathogenic Variants ◽

Newborn Hearing ◽

Genetic Hearing Loss ◽

Sensitivity Specificity

Abstract Background Congenital hearing loss is one of the most common birth defects. Early identification and management play a crucial role in improving patients’ communication and language acquisition. Previous studies demonstrated that genetic screening complements newborn hearing screening in clinical settings. Methods We developed a multiplex PCR amplicon sequencing assay to sequence the full coding region of the GJB2 gene, the most pathogenic variants of the SLC26A4 gene, and hotspot variants in the MT-RNR1 gene. The sensitivity, specificity, and reliability were validated via samples with known genotypes. Finally, a pilot study was performed on 300 anonymous dried blood samples. Results Of 103 samples with known genotypes, the multiplex PCR amplicon sequencing assay accurately identified all the variants, demonstrating a 100% sensitivity and specificity. The consistency is high in the analysis of the test–retest reliability and internal consistency reliability. In the pilot study, 12.3% (37/300) of the newborns were found to carry at least one pathogenic variant, including 24, 10, and 3 from the GJB2, SLC26A4, and MT-RNR1 gene, respectively. With an allele frequency of 2.2%, the NM_004004.6(GJB2):c.109G>A was the most prevalent variant in the study population. Conclusion The multiplex PCR amplicon sequencing assay is an accurate and reliable test to detect hearing loss variants in the GJB2, SLC26A4, and MT-RNR1 genes. It can be used to screen genetic hearing loss in newborns.

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Contribution of the DC:0-3/Axis II: Relationship disorders' diagnostic criteria to detecting infant and toddler abuse and neglect in six European countries: A pilot study - Early diagnosis of infant and toddler abuse and neglect in Portugal: A pilot study

PsycEXTRA Dataset ◽

10.1037/e578482014-048 ◽

2013 ◽

Author(s):

Eunice Magalhaes ◽

Kornilia Hatzinikolaou ◽

M. Manuela Calheiros ◽

M. Clara Barata ◽

Joao Graca ◽

...

Keyword(s):

Pilot Study ◽

Early Diagnosis ◽

Diagnostic Criteria ◽

European Countries ◽

Axis Ii ◽

Abuse And Neglect ◽

Relationship Disorders

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Contribution of the DC:0-3/Axis II: Relationship disorders' diagnostic criteria to detecting infant and toddler abuse and neglect in Spain: A pilot study

PsycEXTRA Dataset ◽

10.1037/e578482014-047 ◽

2013 ◽

Author(s):

Ruth Perez-Robles ◽

Lourdes Ezpeleta

Keyword(s):

Pilot Study ◽

Diagnostic Criteria ◽

Axis Ii ◽

Abuse And Neglect ◽

Relationship Disorders

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Diagnostic difficulties and possibilities of NF1-like syndromes in childhood

BMC Pediatrics ◽

10.1186/s12887-021-02791-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Eva Pinti ◽

Krisztina Nemeth ◽

Krisztina Staub ◽

Anna Lengyel ◽

Gyorgy Fekete ◽

...

Keyword(s):

Diagnostic Criteria ◽

Neurofibromatosis Type ◽

Early Years ◽

Diagnostic Efficiency ◽

Clinical Criteria ◽

Pathogenic Variants ◽

Clinical Diagnostic ◽

Long Time ◽

Diagnostic Difficulties ◽

Clinical Diagnostic Criteria

Abstract Background Neurofibromatosis type 1 (NF1), which is caused by heterozygous inactivating pathogenic variants in the NF1, has poor phenotypic expressivity in the early years of life and there are numerous conditions, including many other tumor predisposition syndromes, that can mimic its appearance. These are collectively termed NF1-like syndromes and are also connected by their genetic background. Therefore, the NF1’s clinical diagnostic efficiency in childhood could be difficult and commonly should be completed with genetic testing. Methods To estimate the number of syndromes/conditions that could mimic NF1, we compiled them through an extensive search of the scientific literature. To test the utility of NF1’s National Institutes of Health (NIH) clinical diagnostic criteria, which have been in use for a long time, we analyzed the data of a 40-member pediatric cohort with symptoms of the NF1-like syndromes’ overlapping phenotype and performed NF1 genetic test, and established the average age when diagnostic suspicion arises. To facilitate timely identification, we compiled strongly suggestive phenotypic features and anamnestic data. Results In our cohort the utility of NF1’s clinical diagnostic criteria were very limited (sensitivity: 80%, specificity: 30%). Only 53% of children with clinically diagnosed NF1 had a detectable NF1 pathogenic variation, whereas 40% of patients without fulfilled clinical criteria tested positive. The average age at first genetic counseling was 9 years, and 40% of children were referred after at least one tumor had already been diagnosed. These results highlight the need to improve NF1-like syndromes’ diagnostic efficiency in childhood. We collected the most extensive spectrum of NF1-like syndromes to help the physicians in differential diagnosis. We recommend the detailed, non-invasive clinical evaluation of patients before referring them to a clinical geneticist. Conclusions Early diagnosis of NF1-like syndromes can help to prevent severe complications by appropriate monitoring and management. We propose a potential screening, diagnostic and management strategy based on our findings and recent scientific knowledge.

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Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽

10.3390/diagnostics11030547 ◽

2021 ◽

Vol 11 (3) ◽

pp. 547

Author(s):

Iolia Akaev ◽

Siavash Rahimi ◽

Olubukola Onifade ◽

Francis John Edward Gardner ◽

David Castells-Rufas ◽

...

Keyword(s):

Ovarian Cancer ◽

Unknown Origin ◽

Parp Inhibitors ◽

Serous Carcinoma ◽

High Grade ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Epithelial Cancers ◽

Pathogenic Variants ◽

Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

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