HLA alleles associated with susceptibility and severity of the COVID-19 in Vietnamese.

The diversity of clinical manifestations in COVID-19 has been observed not only among individuals but also among various populations in globally. HLA molecules play a central role in physiology, protective immunity, and deleterious, disease-related autoimmune reactivity or overreaction. This study exploited the association between HLA frequencies and SARS-CoV-2 susceptibility and disease severity among the Vietnamese cohort (159 patients and 52 controls). A significant difference in frequency of both HLA class I and II in mild, moderate, and severe/fatal COVID-19 patients and negative exposure individuals - the controls were observed. Regarding SARS-CoV-2 sensitivity, HLA-A*03:01, 30:01, HLA-DQA1*01:02, DRB1*15:01, and DRB5*02:02 presented higher frequency in the control group compared with infected patients but DRB1 09:01 frequency was higher in infected patients. Regarding COVID-19 severity, HLA-F*01:01, 01:03 and DPA1*01:03 and 02:01, DPB1*04:01, DQA1*01:02, and DQB1*05:02 alleles were detected with higher frequency in severe patients but DOB*01:01, DRB1*05:01 and 09:01 had a significantly higher frequency in the mild group than remaining groups. Surprisingly, HLA-DQA1*01:02 and DRB1*09:01 alleles were identified with both inversely potential roles in protective function and severe risk. The obtained data herein will contribute to explore on the role of host genetic background in the pathology of COVID-19 disease.

Host Genetic Risk Factors Associated with COVID-19 Susceptibility and Severity in Vietnamese.

Since the emergence and rapid transmission of SARS-CoV-2, numerous scientific reports have searched for the association of host genetic variants with COVID-19, but the data are mostly acquired from Europe. In the current work, we explored the link between host genes (SARS-CoV-2 entry and immune system related to COVID-19 sensitivity/severity) and ABO blood types with COVID-19 from whole-exome data of 200 COVID-19 patients and 100 controls in Vietnam. The O blood type was found to be a protective factor that weakens the worst outcomes of infected individuals. For SARS-CoV-2 susceptibility, rs2229207 (TC genotype, allele C) and rs17860118 (allele T) of IFNAR2 increased the risk of infection, but rs139940581 (CT genotype, allele T) of SLC6A20 reduced virus sensitivity. For COVID-19 progress, the frequencies of rs4622692 (TG genotype) and rs1048610 (TC genotype) of ADAM17 were significantly higher in the moderate group than in the severe/fatal group. The variant rs12329760 (AA genotype) of TMPRSS2 was significantly associated with asymptomatic/mild symptoms. Additionally, rs2304255 (CT genotype, allele T) of TYK2 and rs2277735 (AG genotype) of DPP9 were associated with severe/fatal outcomes. Studies on different populations will give better insights into the pathogenesis, which is ethnic-dependent, and thus decipher the genetic factor's contribution to mechanisms that predispose people to being more vulnerable to COVID-19.

Genetic analyses of Vietnamese patients with oculocutaneous albinism.

BACKGROUND: Oculocutaneous albinism (OCA) is an autosomal recessive disease with hypopigmentation in skin, hair, and eyes, causing by the complete absence or reduction of melanin in melanocytes. Many types of OCA were observed based on the mutation in different causing genes relating to albinism. OCA can occur in non-syndromic and syndromic forms, where syndromic OCA coexists with additional systemic consequences beyond hypopigmentation and visual-associated symptoms. METHODS: We performed whole exome sequencing in seven affected individuals (P1-P7) for mutation identification, and then, Sanger sequencing was used for verifications. RESULTS: Among them, five patients (P1-P5) have mutations on TYR gene including c.346C > T, c.929insC, c.115 T > C, and c.559_560ins25. The mutation on OCA2 and HPS1 genes was found in patient 6 (P6, OCA2 c.2323G > A) and patient 7 (P7, HPS1 c.972delC), respectively. Confirmation in parents (except the family of the elderly patient, P5) showed that the mother and the father in each family carried one of the variants that were detected in patients. Additionally, the effective genetic counseling was applied in the third pregnancy of a family with two OCA children (P1 and P2). CONCLUSION: To our best knowledge, this is the first case with a novel homozygous missense mutation (c.115 T > C, p.W39R) in the TYR gene. This study provides a broader spectrum of mutations linked to the oculocutaneous albinism, an additional scientific basis for diagnosis, and appropriate genetic counseling for risk couples.

Whole exome sequencing revealed novel pathogenic variants in Vietnamese patients with FEVR.

Background: Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder marked by incomplete retinal vascularization associated with exudation, neovascularization, and tractional retinal detachment. FEVR is genetically heterogeneous and is caused by variants in six genes: FZD4, LRP5, NDP, TSPAN12, ZNF408, and CTNNB1. In addition, the phenotypic overlap between FEVR and other disorders has been reported in patients harboring variants in other genes, such as KIF11, ATOH7, and RCBTB1. Purpose: To identify pathogenic variants in Vietnamese pediatric patients diagnosed with FEVR and to investigate the clinical findings in correlation with each causative gene. Methods: A total of 20 probands underwent ocular examinations with fundoscopy (ophthalmoscopy) or fluorescein angiography. Genomic DNA was extracted from the peripheral blood of the probands and their family members. Multiplex ligation-dependent probe amplification (MLPA) was employed to detect copy number variants of FEVR-causing genes. Short variants were screened by whole-exome sequencing (WES) and then validated by Sanger sequencing. Results: Fluorescein angiography showed retinal vascular anomalies in all patients. Other ocular abnormalities commonly found were strabismus, nystagmus, exudation, and retinal detachment. Genetic analysis identified 12 different variants in the FZD4, NDP, KIF11, and ATOH7 genes among 20 probands. Four variants were novel, including FZD4 c.169G>C, p.(G57R); NDP c.175-3A>G, splicing; KIF11 c.2146C>T, p.(Q716*) and c.2511_2515del, p.(N838Kfs*17). All patients with the KIF11 variant showed signs of microcephaly and intellectual disability. The patient with Norrie syndrome and their family members were found to have a deletion of exon 2 in the NDP gene. Conclusions: This study sheds light on the genetic causes of ocular disorders with the clinical expression of FEVR in Vietnamese patients. WES was applied as a comprehensive tool to identify pathogenic variants in complex diseases, such as FEVR, and the detection rate of pathogenic mutations was up to 60%.

Rare and novel variants of PRKN and PINK1 genes in Vietnamese patients with early-onset Parkinson's disease.

BACKGROUND: Early-onset Parkinson's disease (EOPD) refers to that of patients who have been diagnosed or had onset of motor symptoms before age 50, accounting for 4% of Parkinson's disease patients. The PRKN and PINK1 genes, both involved in a metabolic pathway, are associated with EOPD. METHODS: To identify variants associated with EOPD, coding region of PARKIN and PINK1 genes in 112 patients and 112 healthy individuals were sequenced. Multiplex ligation-dependent probe amplification kit was used to determine EOPD patients that carried mutations in PRKN and PINK1 genes. RESULTS AND CONCLUSION: Three rare and three novel mutations in total of 14 variants of PARKIN and PINK1 were detected in the EOPD cohorts. Mutations of PRKN and PINK1 genes were found in five (4.4%) patients, which were four patients with compound heterozygous variants in the PRKN and one case with a homozygous mutation of the PINK1 gene. The novel mutations might reduce the stability of the PRKN and PINK1 protein molecules. The frequency of homozygous mutant genotype p.A340T of the PINK1 in the EOPD cohort was higher than in control (p = 0.0001, OR = 5.704), suggesting this variant might be a risk factor for EOPD. To the best of our knowledge, this is the first study of PRKN and PINK1 genes conducted on Vietnamese EOPD patients. These results might contribute to the genetic screening of EOPD in Vietnam.