Hearing loss is often caused by genetic variants, but for many people, the underlying cause remains unknown, preventing an accurate diagnosis and limiting access to emerging genetic therapies. We performed whole-exome sequencing in more than 1,000 people with hearing loss and integrated the findings with data from their electronic medical records. Despite incomplete clinical information, […]
Latest articles
Founder derivative chromosome causing a recessive-like recurrent disorder: der(17)-associated 19p13.3 duplication in the Upper Tigris Basin (Contributed by Dr. Murat Ozturk)
In this study, we identified the same rare chromosome rearrangement in 15 affected individuals from 11 unrelated families in the Upper Tigris Basin. The rearrangement causes the gain of a small segment of chromosome 19 and the loss of a segment of chromosome 17, resulting in a recognizable pattern of developmental, neurological, and growth-related features. […]
Dual impact of uniparental disomy in imprinting and recessive disorders: a case of UPD(15) with unexpected inheritance and literature review (Contributed by Dr. Sarah Baer)
Our study highlights an unusual way in which one genetic event can cause two different rare diseases in the same child. We describe a boy with Prader-Willi syndrome and Tay-Sachs disease resulting from the inheritance of both copies of chromosome 15 from his mother. Reviewing previous cases showed that similar combinations of genetic diseases can […]
Deletion size and background genetic variation shape congenital heart disease phenotypes in 3016 individuals with 22q11.2 deletion syndrome (Contributed by Dr. Bernice E Morrow)
The clinical presentation of 22q11.2 deletion syndrome (22q11.2DS) is highly variable due to reasons that are not fully understood. Most, but not all, individuals are affected with various types of congenital heart disease (CHD). In our study, we performed a retrospective analysis of data from 3,016 individuals with 22q11.2DS to identify demographic and/or genomic contributors […]
Integrating deep-exome sequencing and droplet digital PCR for genetic diagnosis of 142 patients with somatic overgrowth and vascular malformation (Contributed by Mrs. Karin Sollander)
In this study, we show how it’s possible to increase the diagnostic yield and improve outcome for patients with somatic overgrowth and vascular malformations. These conditions are often caused by genetic variants in a fraction of the individual’s cells, so called mosaicism. Low fraction variants make diagnostics challenging and requires specific laboratory methods. Identifying variants […]
Recurrent helical COL1A1 E678K variant in three families with an EDS-predominant phenotype expanding the clinical and molecular spectrum of COL1-related overlap disorder (Contributed by Dr Shaimaa Helal)
Type I collagen helps give connective tissues their strength. Changes in COL1A1, a gene involved in making this collagen, can cause conditions affecting bones, joints and skin. We describe seven people from three unrelated families with the same COL1A1 variant. They had flexible joints, soft skin and, in some cases, hip dysplasia or dislocation present […]
Clinicopathological, imaging and genetic spectrum of inherited rimmed vacuolar myopathies in a Chinese cohort (Contributed by Dr Feng Lin)
Rimmed vacuoles are small abnormal spaces seen in muscle fibers, but they can occur in many inherited muscle diseases, making diagnosis difficult. We studied 48 patients in China by combining symptoms, muscle imaging, biopsy findings and genetic testing. A genetic diagnosis was reached in 42 patients (87.5%), involving 16 different disease-causing genes. Importantly, rimmed vacuoles […]
Field watch: Rare and common genetic variants shape single-cell immune gene expression
The TenK10K phase 1 study, published in Nature, combines whole-genome sequencing with single-cell RNA sequencing from 5.4 million PBMCs collected from 1,925 people. The researchers examined 28 immune cell types and mapped common regulatory variants for 83% of tested genes, along with rare-variant signals for 47%. Companion studies also analyzed tandem repeats and genetic effects […]
Field watch: AI model predicts developmental brain gene regulation and variant effects
Hao et al. introduced Seal, an interpretable AI model that predicts gene expression and variant effects across 26 brain regions, 30 cell types, and 7 developmental stages. Disease variants often act in specific developmental windows or transient cell populations that are difficult to study directly. It could be particularly useful for interpreting noncoding variants in […]
Field watch: Genome stability during cell migration
A new Nature Cell Biology study examines how embryonic cells protect their DNA while migrating through confined tissue spaces. Cell movement can subject the nucleus to strong mechanical deformation, creating a risk of DNA damage and genome instability. The authors identified a protective mechanism that helps migrating cells preserve nuclear integrity under these stresses. This […]