Human Genomics最新文献

Background: Carrier screening for severe recessive genetic diseases in couples undergoing premarital examinations is a crucial strategy for reducing the incidence of birth defects and promoting reproductive health. However, many high-prevalence but genetically complex diseases cannot be reliably detected using conventional PCR-based methods or short-read next-generation sequencing (NGS).

Results: In this study, 1,203 couples who received free premarital medical examinations at seven units in Shanghai were recruited. PacBio long-read sequencing (LRS) was applied for simultaneous carrier screening of five genetically complex monogenic diseases, including spinal muscular atrophy (SMA), α-/β-thalassemia, congenital adrenal hyperplasia (CAH) (refers to 21-hydroxylase deficiency, 21-OHD), and fragile X syndrome (FXS). A total of 161 individuals were identified as carriers of a single disease, while four individuals carried pathogenic variants associated with two distinct diseases. Four couples were determined to be at high reproductive risk, including one classic CAH family, one SMA family, one hemoglobin H (Hb H) disease family, and one family in which the female was an FXS premutation carrier. In addition, one couple at risk of having a child with non-classic CAH (NCCAH), as well as one male individual with a confirmed diagnosis of NCCAH, were identified.

Conclusions: LRS provides substantial clinical value for comprehensive carrier screening in the premarital population. It enables accurate detection of structural variants and repeat expansions that are often missed by conventional methods. These findings support the integration of LRS into routine premarital genetic screening protocols to enhance early identification of at-risk couples and improve reproductive decision-making.

Background: Gyrate atrophy (GACR), a rare autosomal recessive chorioretinal dystrophy caused by OAT mutations, is genetically and clinically underexplored in multi-ethnic Chinese populations.

Results: Eight patients from five families all exhibited high myopia (mean - 8.28 D), early-onset vision loss, and elevated plasma ornithine. Parapapillary atrophy (PPA) was common (76.92%) and correlated with worse BCVA and longer AL. Four novel OAT mutations were identified: c.213G > A (p.Trp71Ter), c.799 A > C (p.Thr267Pro), c.897 C > A (p.Tyr299Ter) and c.-30 + 22_-30 + 43del. Minigene assays confirmed aberrant splicing for the latter.

Conclusions: This study identifies the first pathogenic 5' UTR variant in GACR, reveals ethnic-specific mutation profiles, and underscores PPA as a severity-linked feature.

Background: Recent studies have shown that unhealthy sleep behaviors are associated with chronic liver disease. However, the association of sleep patterns and genetic susceptibility with the incidence of cirrhosis remains inadequately elucidated.

Methods: This study included 364,308 participants initially free of liver cirrhosis from the UK Biobank. Sleep patterns were derived based on five self-reported sleep behaviors, including sleep duration, chronotypes, insomnia, snoring, and daytime sleepiness. Additionally, a polygenic risk score for cirrhosis was constructed for each participant. Cox regression models were utilized to estimate the hazard ratio (HR) and 95% confidence interval (CI) of cirrhosis associated with sleep patterns and polygenic risk score.

Results: During a median follow-up of 12.6 years, we recorded 1,814 cirrhosis events. Compared with healthy sleep patterns, the HRs (95% CI) for moderate and poor sleep patterns were 1.27 (95% CI: 1.14-1.42) and 1.73 (95% CI: 1.45-2.08), respectively. A joint effect of sleep and genetic factors on cirrhosis risk was observed, with HR reaching 3.50 (95% CI: 2.42-5.06) with poor sleep patterns and high genetic risk compared with those with healthy sleep patterns and low genetic risk. In addition, the high genetic risk for participants, poor sleep patterns of standardized decade liver cirrhosis were 0.49%, as opposed to 0.30% for those with healthy sleep patterns. The same trend was witnessed in individuals at low genetic risk.

Conclusions: Our results show that the healthy sleep patterns are associated with a lower risk of incident liver cirrhosis, especially in individuals with high genetic susceptibility.