The implementation of genome sequencing in rare genetic diseases diagnosis: a pilot study from the Hong Kong genome project.

Background: Genome sequencing (GS) has revolutionised the diagnostic odyssey of patients with rare genetic diseases (RDs) and accelerated large-scale genome projects globally. However, the impact of GS on patients with RDs is yet to be investigated among genome projects in Asia. The Hong Kong Genome Project (HKGP) was implemented to benefit patients and families with RDs in Hong Kong, and to increase the inclusiveness of Chinese genomic data.

Molecular genetic diagnosis and surgical management in a cohort of children with 46,XY disorders/differences of sex development.

Objective: A firm diagnosis revealing the etiology of disorders/differences of sex development (DSD) is most helpful in guiding clinical management. The aim of this study is to investigate molecular genetic diagnoses and surgical treatment in a cohort of children with 46,XY DSD.

Methods: A retrospective study was conducted on children with 46,XY DSD.

The effects of HPV oncoproteins on host communication networks: Therapeutic connotations.

Human papillomavirus (HPV) infections are a leading cause of viral-induced malignancies worldwide, with a prominent association with cervical and head and neck cancers. The pivotal role of HPV oncoproteins, E5, E6, and E7, in manipulating cellular events, which contribute to viral pathogenesis in various ways, has been extensively documented. This article reviews the influence of HPV oncoproteins on cellular signaling pathways within the host cell, shedding light on the underlying molecular mechanisms.

A Baby With Complete Androgen Insensitivity Syndrome and the Fortuitous Discovery of 45,X/46,XY Mosaicism.

Disorders of sex development (DSD) are caused by defects in the complex sexual differentiation cascade, resulting in discordance among an individual's genetic, gonadal, and genital sexes. It affects one in 4,500 live births. A wide spectrum of genital phenotypes can be found depending on the underlying pathogenic mechanism and the developmental stage that is affected.

The ubiquitin specific protease 7 stabilizes HPV16E7 to promote HPV-mediated carcinogenesis.

Human papillomavirus (HPV) encoded E7 oncoprotein plays an important role in supporting the viral productive cycle and inducing cancer phenotypes. The ability of E7 to exercise these functions, partly, depends upon its steady-state level. HPV manipulates the host de-ubiquitination pathway to maintain the stability of its viral proteins.

Public and Healthcare Provider Receptivity toward the Retention of Dried Blood Spot Cards and Their Usage for Extended Genetic Testing in Hong Kong.

Dried blood spot (DBS) cards from newborn screening (NBS) programs represent a wealth of biological data. They can be stored easily for a long time, have the potential to support medical and public health research, and have secondary usages such as quality assurance and forensics, making it the ideal candidate for bio-banking. However, worldwide policies vary with regard to the duration of storage of DBS cards and how it can be used.

Prenatal diagnosis of Myhre syndrome with a heterozygous pathogenic variant in SMAD4 gene presented with thick nuchal translucency and cardiac abnormalities.

Prenatal testing was performed in a 39-year-old Chinese pregnant woman referred for increased nuchal translucency measuring 5.7 mm. Non-invasive prenatal testing and SNP array study on amniotic fluid samples were normal.

Fibrodysplasia ossificans progressiva in Hong Kong-A case report series.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare condition. The diagnosis could be challenging due to its rarity and non-specific presenting symptoms. However, early diagnosis and appropriate management help in preserving patients' function and quality of life.

Interaction between Human Papillomavirus-Encoded E6 Protein and AurB Induces Cell Immortalization and Proliferation-A Potential Target of Intervention.

The human papillomavirus E6 and E7 oncoproteins interact with a different subset of host proteins, leading to dysregulation of the apoptotic, cell cycle, and signaling pathways. In this study, we identified, for the first time, that Aurora kinase B (AurB) is a interacting partner of E6. We systematically characterized the AurB-E6 complex formation and its consequences in carcinogenesis using a series of and cell-based assays.

E6-Encoded by Cancer-Causing Human Papillomavirus Interacts with Aurora Kinase A To Promote HPV-Mediated Carcinogenesis.

The expression of human papillomavirus (HPV) oncoproteins perturbed multiple cellular events of the host cells, leading to the formation of cancer phenotypes. Our current and previous studies indicated that Aurora kinase A (AurA), a mitotic regulator that is often aberrantly expressed in human cancers, is preferentially bound to E6-encoded by cancer-causing HPV. AurA is believed to be important for the proliferation and survival of HPV-positive cells.

Implementation of Public Funded Genome Sequencing in Evaluation of Fetal Structural Anomalies.

With the advancements in prenatal diagnostics, genome sequencing is now incorporated into clinical use to maximize the diagnostic yield following uninformative conventional tests (karyotype and chromosomal microarray analysis). Hong Kong started publicly funded prenatal genomic sequencing as a sequential test in the investigation of fetal structural anomalies in April 2021. The objective of the study was to evaluate the clinical performance and usefulness of this new service over one year.

Review of the Standard and Advanced Screening, Staging Systems and Treatment Modalities for Cervical Cancer.

Cancer arising from the uterine cervix is the fourth most common cause of cancer death among women worldwide. Almost 90% of cervical cancer mortality has occurred in low- and middle-income countries. One of the major aetiologies contributing to cervical cancer is the persistent infection by the cancer-causing types of the human papillomavirus.

Investigation of Chromosomal Structural Abnormalities in Patients With Undiagnosed Neurodevelopmental Disorders.

Structural variations (SVs) are various types of the genomic rearrangements encompassing at least 50 nucleotides. These include unbalanced gains or losses of DNA segments (copy number changes, CNVs), balanced rearrangements (such as inversion or translocations), and complex combinations of several distinct rearrangements. SVs are known to play a significant role in contributing to human genomic disorders by disrupting the protein-coding genes or the interaction(s) with cis-regulatory elements.

Detecting structural variations with precise breakpoints using low-depth WGS data from a single oxford nanopore MinION flowcell.

Structural variation (SV) is a major cause of genetic disorders. In this paper, we show that low-depth (specifically, 4×) whole-genome sequencing using a single Oxford Nanopore MinION flow cell suffices to support sensitive detection of SV, particularly pathogenic SV for supporting clinical diagnosis. When using 4× ONT WGS data, existing SV calling software often fails to detect pathogenic SV, especially in the form of long deletion, terminal deletion, duplication, and unbalanced translocation.

Oesophageal carcinoma: The prevalence of DNA tumour viruses and therapy.

Oesophageal carcinoma ranks the sixth leading cause of cancer death and affected 544,000 - 604,000 people in 2020. Patients often presented with a poor cancer prognosis with a low survival rate of 15-25%. Depending upon the cell type, oesophageal carcinoma is categorised into oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC).

Temporal-Geographical Dispersion of SARS-CoV-2 Spike Glycoprotein Variant Lineages and Their Functional Prediction Using Approach.

SARS-CoV-2 is a positive-sense single-stranded RNA virus with emerging mutations, especially on the Spike glycoprotein (S protein). To delineate the genomic diversity in association with geographic dispersion of SARS-CoV-2 variant lineages, we collected 939,591 complete S protein sequences deposited in the Global Initiative on Sharing All Influenza Data (GISAID) from December 2019 to April 2021. An exponential emergence of S protein variants was observed since October 2020 when the four major variants of concern (VOCs), namely, alpha (α) (B.

Erratum: Erratum: Encephalopathy and Responsiveness to Pyridoxal-5'-Phosphate.

[This corrects the article DOI: 10.1055/s-0040-1721384.].

A Fetus with Congenital Microcephaly, Microphthalmia and Cataract Was Detected with Biallelic Variants in the Gene: A Case Report.

Microcephaly and microphthalmia are both rare congenital abnormalities, while concurrently, these two are even rarer. The underlying etiology would be complex interplaying between heterogeneous genetic background and the environmental pathogens, particularly during critical periods of early tissue development. Here, we reported a prenatal case with microcephaly, microphthalmia, and bilateral cataracts detected by ultrasonography and confirmed by autopsy.

Prenatal phenotype of Kabuki syndrome: A case series and literature review.

Objectives: Kabuki syndrome (KS) is a genetic disorder characterized by intellectual disability, facial dysmorphism and congenital anomalies. We aim to investigate the prenatal features of fetuses with KS and to provide a comprehensive review of the literature on prenatal sonographic abnormalities associated with KS.

Methods: We retrospectively reviewed the prenatal ultrasound findings of all mothers of children with molecularly confirmed KS in Hong Kong, between 1991 and 2019.

Clinical and molecular characterization study of Chinese Kabuki syndrome in Hong Kong.

Kabuki syndrome (OMIM #147920 and 300867) is a rare genetic disorder characterized by a distinctive facial gestalt, intellectual disability and multiple congenital anomalies. We summarized the clinical features and molecular findings of the Kabuki syndrome (KS) patients diagnosed in Hong Kong between January 1991 and December 2019. There were 21 molecularly confirmed KS.

Encephalopathy and Responsiveness to Pyridoxal-5'-Phosphate.

mutations encompass a wide range of phenotypes, ranging from benign familial neonatal seizure to a clinical spectrum of early-onset epileptic encephalopathy that occurs in the early neonatal period. We report an infant with encephalopathy presenting as neonatal seizure, initially controlled by two anticonvulsants. Electroencephalogram (EEG) showed repetitive multifocal epileptiform discharges, which remained similar after administration of intravenous pyridoxine injection.

Prenatal and postnatal diagnosis of Schuurs-Hoeijmakers syndrome: Case series and review of the literature.

Schuurs-Hoeijmakers syndrome (SHS) is a rare syndrome involving a de novo variant in the PACS1 gene on chromosome 11q13. There are 36 individuals published in the literature so far, mostly diagnosed postnatally (34/36) after recognizing the typical facial features co-occurring with developmental delay, intellectual disability, and multiple malformations. Herein, we present one prenatal and 15 postnatal cases with the recurrent heterozygous pathogenic variant NM_018026.

Prenatal diagnosis and long-term follow-up of a Chinese patient with mosaic variegated aneuploidy and its molecular analysis.

Mosaic variegated aneuploidy (MVA) is a rare genetic disorder caused by mutations in , or . We describe the prenatal diagnosis, molecular characterization, and clinical management of a long-lived patient with -related MVA.

Cost-effectiveness analysis of chromosomal microarray as a primary test for prenatal diagnosis in Hong Kong.

Background: Chromosomal microarray (CMA) has been shown to be cost-effective over karyotyping in invasive prenatal diagnosis for pregnancies with fetal ultrasound anomalies. Yet, information regarding preceding and subsequent tests must be considered as a whole before the true cost-effectiveness can emerge. Currently in Hong Kong, karyotyping is offered free as the standard prenatal test while genome-wide array comparative genome hybridization (aCGH), a form of CMA, is self-financed.

Phenotypic and mutational spectrum of 21 Chinese patients with Alström syndrome.

Alström syndrome (AS) is a monogenic syndromic ciliopathy caused by mutations in the ALMS1 (Alström Syndrome 1) gene. A total of 21 subjects with AS from 20 unrelated Chinese families were recruited. Our cohort consists of 9 females and 12 males, between 5 months and 20 years old.