Host genetic polymorphisms involved in long-term symptoms of COVID-19.

Host genetic polymorphisms are recognized as a critical determinant of diversity in clinical symptoms of Coronavirus disease 2019 (COVID-19). Accordingly, this study aimed to determine possible associations between single nucleotide polymorphisms (SNPs) in 37 candidate genetic variants and clinical consequences of COVID-19 - especially long-term symptoms, Long COVID. A total of 260 COVID-19 patients, divided into mild (n = 239) and severe (n = 21) and further categorized based on the presence of Long COVID (no, n = 211; yes, n = 49), were recruited. Genotyping of selected polymorphisms responsible for viral entry, immune response, and inflammation was performed using MassARRAY system. Out of 37 SNPs, 9 including leucine zipper transcription factor like-1 (LZTFL1) rs10490770 C allele, LZTFL1 rs11385942 dupA allele, nicotinamide adenine dinucleotide synthetase-1 (NADSYN1) rs12785878 TT genotype, plexin A-4 (PLXNA4) rs1424597 AA genotype, LZTFL1 rs17713054 A allele, interleukin-10 (IL10) rs1800896 TC genotype and C allele, angiotensin converting enzyme-2 (ACE2) rs2285666 T allele, and plasmanylethanolamine desaturase-1 (PEDS1) rs6020298 GG genotype and G allele were significantly associated with an increased risk of developing Long COVID, whereas interleukin-10 receptor subunit beta (IL10RB) rs8178562 GG genotype was significantly associated with a reduced risk of Long COVID. Kaplan-Meier curve displayed that the above gene polymorphisms were significantly associated with cumulative rate of Long COVID occurrence. Polymorphisms in LZTFL1 rs10490770, LZTFL1 rs11385942, LZTFL1 rs17713054, NADSYN1 rs12785878, PLXNA4 rs1424597, IL10 rs1800896, ACE2 rs2285666, PEDS1 rs6020298, and IL10RB rs8178562 appear to be genetic factors involved in development of Long COVID.

Cost-minimization analysis of sequential genetic testing versus targeted next-generation sequencing gene panels in patients with pheochromocytoma and paraganglioma.

INTRODUCTION: Pheochromocytomas and paragangliomas (PPGLs) are highly heritable tumours, with up to 40% of cases carrying germline variants. Current guidelines recommend genetic testing for all patients with PPGLs. Next-generation sequencing (NGS) enables accurate, fast, and inexpensive genetic testing. This study aimed to compare the costs related to PPGL genetic testing between the sequential testing using the decisional algorithm proposed in the 2014 Endocrine Society guidelines and targeted NGS gene panels. METHODS: Patients with proven PPGLs were enrolled. A gene list covering 17 susceptibility genes related to hereditary PPGLs was developed for targeted sequencing. Validation was carried out by Sanger sequencing. We simulated the diagnostic workflow to examine the anticipated costs based on each strategy for genetic testing. RESULTS: Twenty-nine patients were included, among whom a germline variant was identified in 34.5%. A total of 22.7% with apparently sporadic PPGL carried a variant. Five genes were involved (RET, n = 3; SDHB, n = 3; SDHD, n = 2; EGLN1, n = 1; and NF1, n = 1). According to the diagnostic workflow, the average cost of the targeted NGS (534.7 US dollars per patient) is lower than that of the sequential testing (734.5 US dollars per patient). The targeted NGS can also reduce the number of hospital visits from 4.1 to 1 per person. The cost can be further reduced to 496.24 US dollars per person (32% reduction) if we apply a new syndromic-driven diagnostic algorithm to establish priorities for specific genetic testing for syndromic and selected cases, and targeted NGS for non-syndromic patients. CONCLUSIONS: Targeted NGS can reduce both the cost of PPGL genetic testing and the number of hospital visits, compared with the conventional approach. Our proposed algorithm is the preferred approach due to its significant reduction of the cost of genetic testing.Key messagePheochromocytomas and paragangliomas are highly heritable neoplasms.The targeted next-generation sequencing (NGS) gene panels have proven to be fast, accurate, and inexpensive for the genetic analysis.According to this cost analysis, it is economically reasonable to use targeted NGS gene panels for genetic screening.

Genomic surveillance of SARS-CoV-2 in Thailand reveals mixed imported populations, a local lineage expansion and a virus with truncated ORF7a.

Coronavirus Disease 2019 (COVID-19) is a global public health threat. Genomic surveillance of SARS-CoV-2 was implemented in March of 2020 at a major diagnostic hub in Bangkok, Thailand. Several virus lineages supposedly originated in many countries were found, and a Thai-specific lineage, designated A/Thai-1, has expanded to be predominant in Thailand. A virus sample in the SARS-CoV-2 A/Thai-1 lineage contains a frame-shift deletion at ORF7a, encoding a putative host antagonizing factor of the virus.

DUOX2 variants are a frequent cause of congenital primary hypothyroidism in Thai patients.

OBJECTIVE: To identify the genetic etiologies of congenital primary hypothyroidism (CH) in Thai patients. DESIGN AND METHODS: CH patients were enrolled. Clinical characteristics including age, signs and symptoms of CH, pedigree, family history, screened thyroid-stimulating hormone results, thyroid function tests, thyroid imaging, clinical course and treatment of CH were collected. Clinical exome sequencing by next-generation sequencing was performed. In-house gene list which covered 62 potential candidate genes related to CH and thyroid disorders was developed for targeted sequencing. Sanger sequencing was performed to validate the candidate variants. Thyroid function tests were determined in the heterozygous parents who carried the same DUOX2 or DUOXA2 variants as their offsprings. RESULTS: There were 118 patients (63 males) included. Mean (SD) age at enrollment was 12.4 (7.9) years. Forty-five of 118 patients (38%) had disease-causing variants. Of 45 variants, 7 genes were involved (DUOX2, DUOXA2, TG, TPO, SLC5A5, PAX8 and TSHR). DUOX2, a gene causing thyroid dyshormonogenesis, was the most common defective gene (25/45, 56%). The most common DUOX2 variant found in this study was c.1588A>T. TG and TPO variants were less common. Fourteen novel variants were found. Thyroid function tests of most parents with heterozygous state of DUOX2 and DUOXA2 variants were normal. CONCLUSIONS: DUOX2 variants were most common among Thai CH patients, while TG and TPO variants were less common. The c.1588A>T in DUOX2 gene was highly frequent in this population.