- Theoretical result: A total of 17 patient samples from individuals with one of five rare diseases, as well as 44 samples from their family members, were successfully collected and subjected to DNA extraction. DNA libraries were constructed and whole exome sequencing (WES) was performed on all 17 samples from patients with rare diseases. Variant filtering and analysis identified 324 variants in genes associated with the five disease groups. Of these, 19 pathogenic variants in 17 genes were confirmed to be inherited within families by Sanger sequencing.

• Skeletal dysplasia: Five pathogenic variants were identified in five genes across five patient families: BAAT (c.388dupA, p.Arg130Lysfs12); FGFR3 (c.1626C>G, p.Asn542Lys); RUNX2 (c.673C>T, p.Arg225Trp); PHEX (c.1399G>T, p.Glu467); and FGFR2 (c.755C>G, p.Ser252Trp).

• Disorders of sex development: Three pathogenic variants were detected in three genes within one patient family: AKR1C3 (c.15C>G, p.His5Gln); DOCK8 (c.2953T>C, p.Phe985Leu); and POR (c.1508C>T, p.Ala503Val).

• Pituitary insufficiency: Two pathogenic variants were identified in two genes across three patient families: POU1F1 (c.811C>T, p.Arg271Trp) and CDH7 (c.5428C>T, p.Arg1810*).

• Microcephaly with congenital anomalies: Three pathogenic variants were found in two genes in two patient families: AARS2 (c.452T>C, p.Met151Thr; c.872C>T, p.Pro291Leu) and HPDL (c.769C>A, p.Gln257Lys).

• Leukodystrophies: Five pathogenic variants were identified in two genes across three patient families: LAMA2 (c.4717+5G>A, c.7156-5_7157delinsT p.Arg2386*, c.198C>A p.Tyr66*); and PANK2 (c.1351C>T p.Arg451Ter, c.856C>T p.Arg286Cys).

- Applied results: The sequencing results and identification of pathogenic variants provide physicians with valuable information for diagnosing, managing and treating patients with rare diseases, as well as for providing genetic counselling. In particular, these findings support clinicians in offering reproductive counselling to families with a child affected by a genetic disorder who are considering having additional children. Furthermore, the results contribute to the development of a national database on genotype–phenotype correlations of rare diseases and syndromes in the Vietnamese population.

- A novel homozygous frameshift mutation (c.388dupA, p.R130Kfs*12) in the BAAT gene was identified in a female patient diagnosed with skeletal dysplasia.

- A novel homozygous mutation (c.769C>A, p.Gln257Lys) in the HPDL gene was identified in the first Vietnamese patient diagnosed with microcephaly accompanied by congenital anomalies.

- A novel compound heterozygous mutation (c.856C>T, p.Arg286Cys and c.1351C>T, p.Arg451Ter) in the PANK2 gene was identified in the first Vietnamese patient diagnosed with PKAN (Pantothenate Kinase-Associated Neurodegeneration). This case marks a significant milestone as the first confirmed PKAN case reported in Vietnam.

- A novel complex mutation (c.7156-5_7157delinsT, p.Arg2386*) in the LAMA2 gene was identified in a patient with leukodystrophy.

Science and technology outputs: A series of reports on five datasets concerning coding regions and pathogenic variants associated with five rare diseases has been finalised. These datasets are specifically related to:

+ One dataset of coding regions and pathogenic variants from five patients with skeletal dysplasia.

+ One dataset of coding regions and pathogenic variants from three patients with disorders of sex development.

+ A dataset of coding regions and pathogenic variants from three patients with pituitary insufficiency.

+ A dataset of coding regions and pathogenic variants from three patients with microcephaly accompanied by congenital anomalies; and a dataset of coding regions and pathogenic variants from three patients with pituitary insufficiency.

+ A further dataset comprised coding regions and pathogenic variants from three patients with leukodystrophies.

Scientific publications: A total of four scientific articles have been published in international journals, including: Two articles in Medicine; one article in the International Journal of Molecular Sciences; and one article in Frontiers in Genetics. Additionally, two articles have been published in national peer-reviewed journals: One in the Journal of Biotechnology and one presented at a scientific conference.

- Four articles have been published in reputable international journals that are indexed in the Science Citation Index Expanded (SCIE).

+ Van Khanh Tran, Chi Dung Vu, Hai Anh Tran, Nguyen Thi Kim Lien, Nguyen Van Tung, Nguyen Ngoc Lan, Huy Thinh Tran, Nguyen Huy Hoang. The first Vietnamese patient who presented late onset of pantothenate kinase-associated neurodegeneration diagnosed by whole exome sequencing: A case report. Medicine, 2023. 102(43): e34853

+ Duc Quan Nguyen, Thi Bich Ngoc Can, Chi Dung Vu, Thi Anh Thuong Tran, Ngoc Lan Nguyen, Thi Kim Lien Nguyen, Van Tung Nguyen, Thanh Hien Nguyen, Thi Huong Giang Tran, Huy Hoang Nguyen. Identifcation of a novel BAAT frameshift mutation in a female child diagnosed with skeletal dysplasia: A case report. Medicine, 2024. 103 (36): e39509

+ Van Khanh Tran, Ngoc-Lan Nguyen, Lan Ngoc Thi Tran, Phuong Thi Le, Anh Hai Tran, Tuan L. A. Pham, Nguyen Thi Kim Lien, Nguyen Thi Xuan, Le Tat Thanh, Thanh Van Ta, Thinh Huy Tran and Huy-Hoang Nguyen. Merosin-deficient congenital muscular dystrophy type 1a: detection of LAMA2 variants in Vietnamese patients. Frontiers in Genetic, 2023. 1183663

+ Ha Thu Nguyen, Khanh Ngoc Nguyen, Tran Minh Dien, Thi Bich Ngoc Can, Thi Thanh Ngan Nguyen, Nguyen Thi Kim Lien , Nguyen Van Tung, Nguyen Thi Xuan , Nguyen Thien Tao, Ngoc Lan Nguyen, Van Khanh Tran, Tran Thi Chi Mai, Van Anh Tran, Huy Hoang Nguyen and Chi Dung Vu. Identification of POU1F1 variants in Vietnamses patients with combined pituitary hormone deficiency. International Journal of Molecular Sciences, 2025. 26(6).2406

- One article was published in a reputable national journal.

+ Duc Tien Nguyen, Thi Thanh Ngan Nguyen, Ngoc Lan Nguyen, Thi Anh Thuong Tran, Thi Bich Ngoc Can, Chi Dung Vu, Van Tung Nguyen, Thi Kim Lien Nguyen, Thanh Hien Nguyen, Duc Quan Nguyen, Thi Huong Giang Tran, Ke Long Phan and Huy Hoang Nguyen. Whole exome sequencing identified a pathogenic variant c.1620C>G in the FGFR3 gene in a Vietnamese patient. Vietnam Journal of Biotechnology, 2025. 23(1). 13-23

- One article presented at a scientific conference

+ Nguyễn Hoàng Thanh Trang, Nguyễn Ngọc Lan, Cấn Thị Bích Ngọc, Trần Thị Anh Thương, Vũ Chí Dũng, Nguyễn Thị Kim Liên, Nguyễn Văn Tụng, Lê Quang Tuấn, Nguyễn Đức Quân, Nguyễn Thanh Hiền, Trần Thị Hương Giang, Nguyễn Thị Thanh Ngân, Nguyễn Huy Hoàng. Giải trình tự toàn bộ vùng mã hóa trên bệnh nhân mắc loạn sản xương. Hội nghị Công nghệ sinh học toàn quốc. 2023

Supported the training of two PhD candidates, whose research topics and supervisors were officially approved by Decision 756/QĐ-HVKHCN, issued by the Director of Academy of Science and Technology on 28 June 2024; and by Decision 6758/QĐ-ĐHYHN, issued by the Rector of Hanoi Medical University on 29 December 2022.