Explanipedia

Rhabdomyolysis in the Era of Next-Generation Sequencing: Selecting Patients with a High Likelihood of a Genetic Susceptibility Using ‘RHABDO’ Features Open

Nick Kruijt, Sanne A. J. H. van de Camp, Jasper J. Kramer, Luuk R. van den Bersselaar, Meyke Schouten , et al. · 2025

Background/Objectives: Rhabdomyolysis is a potentially life-threatening condition characterized by acute skeletal muscle breakdown. In addition to well-described external triggers, a genetic contribution is increasingly recognized. We aime…

Interrupted CTG repeats in the 37–43 units size range in the 3ʹUTR of DMPK are common alleles Open

Hilde Swinkels, Maike Leferink, Maartje Pennings, Bart van der Sanden, Jordi Corominas Galbany , et al. · 2025

Missense variants inTUBA4Acause myo-tubulinopathies Open

Mridul Johari, Chiara Folland, Yoshihiko Saito, Machteld M. Oud, J. Parmar , et al. · 2025

Tubulinopathies encompass a wide spectrum of disorders resulting from variants in genes encoding α- and β-tubulins, the key components of microtubules. While previous studies have linked de novo or dominantly inherited TUBA4A missense vari…

Pathogenic variants inBORCS5Cause a Spectrum of Neurodevelopmental and Neurodegenerative Disorders with Lysosomal Dysfunction Open

Niccolò E. Mencacci, Georgia Minakaki, Reza Maroofian, Raffaella De Pace, Adeline Paimboeuf , et al. · 2025

BORCS5 encodes a subunit of the BLOC-one-related complex (BORC), which is known to mediate the kinesin-dependent anterograde movement of lysosomes. Using whole-exome sequencing, we identified 12 cases from seven families carrying bi-alleli…

Optical genome mapping enables accurate testing of large repeat expansions Open

Bart van der Sanden, Kornelia Neveling, Syukri Shukor, Michael D. Gallagher, Joyce Lee , et al. · 2025

Short tandem repeats (STRs) are common variations in human genomes that frequently expand or contract, causing genetic disorders, mainly when expanded. Traditional diagnostic methods for identifying these expansions, such as repeat-primed …

Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum Open

Sandra Coppens, Nicolas Deconinck, Patricia A. Sullivan, Andrei Smolnikov, Joshua S. Clayton , et al. · 2025

Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders. Objective To better understand the presentation and clinical needs of the under‐characterized extreme end of the congenital titinopathy seve…

Delayed Progression of Ataxia with a Static Cerebellar Lesion– Consider SCA27B Open

Tsz Hang Wong, Jamie Manuputty, Tom van Seeters, Erik‐Jan Kamsteeg, Bart van de Warrenburg · 2025

Repeat expansions in the fibroblast growth factor 14 gene ( FGF14 ), associated with spinocerebellar ataxia type 27B (SCA27B), have emerged as a prevalent cause of previously unexplained late-onset cerebellar ataxia. Here, we present a pat…

Pathogenicity assessment of seven RYR1 variants in patients with confirmed susceptibility to malignant hyperthermia in the Netherlands Open

Luuk R. van den Bersselaar, Anja Schiemann, Chu-Ya Yang, Nicol C. Voermans, Ignacio Malagon , et al. · 2025

The variants p.Glu342Lys, p.Leu2288Ser p.Phe2340Leu, and p.Arg2676Trp are pathogenic or likely pathogenic for MH and can be used for presymptomatic testing for MH susceptibility. As current knowledge on the p.Val3324Ala, p.Phe4076Leu, and …

Correction: A 5-year natural history study in LAMA2-related muscular dystrophy and SELENON-related myopathy: the Extended LAST STRONG study Open

E. C. M. de Laat, S.L.S. Houwen- van Opstal, Karlijn Bouman, Jeroen L. M. van Doorn, Donnie Cameron , et al. · 2024

Nemaline Myopathy Type 6 Caused by Variants in the KBTBD13 Gene Open

Esmee S.B. van Kleef, Karlijn Bouman, J. Molenaar, Benno Küsters, Jan T. Groothuis , et al. · 2024

This cross-sectional study in patients with NEM6 shows a relatively mild clinical phenotype and mildly abnormal functional tests. However, patients report an important impact on the daily activities, which is illustrated by functional diff…

Multisample motif discovery and visualization for tandem repeats Open

Yaran Zhang, Marc Hulsman, Alex Salazar, Niccoló Tesi, Lydian Knoop , et al. · 2024

Tandem repeats (TRs) occupy a significant portion of the human genome and are a source of polymorphisms due to variations in sizes and motif compositions. Some of these variations have been associated with various neuropathological disorde…

A 5-year natural history study in LAMA2-related muscular dystrophy and SELENON-related myopathy: the Extended LAST STRONG study Open

E. C. M. de Laat, S.L.S. Houwen- van Opstal, Karlijn Bouman, Jeroen L. M. van Doorn, Donnie Cameron , et al. · 2024

Characterizing tandem repeat complexities across long-read sequencing platforms with TREAT and otter Open

Niccoló Tesi, Alex Salazar, Yaran Zhang, Sven J. van der Lee, Marc Hulsman , et al. · 2024

Tandem repeats (TRs) play important roles in genomic variation and disease risk in humans. Long-read sequencing allows for the accurate characterization of TRs; however, the underlying bioinformatics perspectives remain challenging. We pre…

Monoallelic de novo AJAP1 loss-of-function variants disrupt trans-synaptic control of neurotransmitter release Open

Simon Früh, Sami Boudkkazi, Peter Koppensteiner, Vita Sereikaité, Li‐Yuan Chen , et al. · 2024

Adherens junction–associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), w…

A New Case Series Suggests That SCA48 (ATX/STUB1) Is Primarily a Monogenic Disorder Open

Teije van Prooije, Maartje Pennings, Lucille D.A. Dorresteijn, Thatjana Gardeitchik, Vincent J.J. Odekerken , et al. · 2024

Background Monoallelic, pathogenic STUB1 variants cause autosomal dominant cerebellar ataxia (ATX‐ STUB1 /SCA48). Recently, a genetic interaction between STUB1 variants and intermediate or high‐normal CAG/CAA repeats in TBP was suggested, …

Optical Genome Mapping for Applications in Repeat Expansion Disorders Open

Bart van der Sanden, Kornelia Neveling, Andy Wing Chun Pang, Syukri Shukor, Michael D. Gallagher , et al. · 2024

Short tandem repeat (STR) expansions are associated with more than 60 genetic disorders. The size and stability of these expansions correlate with the severity and age of onset of the disease. Therefore, being able to accurately detect the…

The expanding clinical and genetic spectrum of DYNC1H1-related disorders Open

Birk Möller, Lena‐Luise Becker, Afshin Saffari, Alexandra Afenjar, Emanuele G. Coci , et al. · 2024

Intracellular trafficking involves an intricate machinery of motor complexes, including the dynein complex, to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains, as well as cytoplasmic light and interme…

Maternal cell contamination in postnatal umbilical cord blood samples implies a low risk for genetic misdiagnoses Open

Sanne P. Smeekens, Maike Leferink, Helger G. Yntema, Erik‐Jan Kamsteeg · 2024

Objective Maternal cell contamination (MCC) poses a risk for misdiagnosis in prenatal genetic testing, and is examined in accredited diagnostic laboratories However, the awareness of possible MCC in perinatal/postnatal genetic testing, mai…

Optical genome mapping enables accurate repeat expansion testing Open

Bart van der Sanden, Kornelia Neveling, Syukri Shukor, Michael D. Gallagher, Joyce Lee , et al. · 2024

Short tandem repeats (STRs) are amongst the most abundant class of variations in human genomes and are meiotically and mitotically unstable which leads to expansions and contractions. STR expansions are frequently associated with genetic d…

Characterising tandem repeat complexities across long-read sequencing platforms with TREAT and otter Open

Niccoló Tesi, Alex Salazar, Yaran Zhang, Sven J. van der Lee, Marc Hulsman , et al. · 2024

Tandem repeats (TR) play important roles in genomic variation and disease risk in humans. Long-read sequencing allows for the accurate characterisation of TRs, however, the underlying bioinformatics perspectives remain challenging. We pres…

MotifScope: a multi-sample motif discovery and visualization tool for tandem repeats Open

Yaran Zhang, Marc Hulsman, Alex Salazar, Niccoló Tesi, Lydian Knoop , et al. · 2024

Tandem repeats (TRs) constitute a significant portion of the human genome, exhibiting high levels of polymorphism due to variations in size and motif composition. These variations have been associated with various neuropathological disorde…

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy Open

Ana Töpf, Dan Cox, Irina Zaharieva, Valeria Di Leo, J. Sarparanta , et al. · 2024

Genome sequencing as a generic diagnostic strategy for rare disease Open

Gaby Schobers, Ronny Derks, Amber den Ouden, Hilde Swinkels, Jeroen van Reeuwijk , et al. · 2024

The FGF14 gene is a milestone in ataxia genetics Open

Bart P.C. van de Warrenburg, Erik‐Jan Kamsteeg · 2024

Correction: Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples Open

Robin Wijngaard, German Demidov, Luke O’Gorman, Jordi Corominas‐Galbany, Burcu Yaldız , et al. · 2023

A Novel Variant in TPM3 Causing Muscle Weakness and Concomitant Hypercontractile Phenotype Open

Katarzyna Robaszkiewicz, Małgorzata Siatkowska, Renske I. Wadman, Erik‐Jan Kamsteeg, Zhiyong Chen , et al. · 2023

A novel variant of unknown significance c.8A > G (p.Glu3Gly) in TPM3 was detected in two unrelated families. TPM3 encodes the transcript variant Tpm3.12 (NM_152263.4), the tropomyosin isoform specifically expressed in slow skeletal muscle …

Systematic analysis of paralogous regions in 41,755 exomes uncovers clinically relevant variation Open

Wouter Steyaert, Lonneke Haer‐Wigman, Rolph Pfundt, Debby M.E.I. Hellebrekers, Marloes Steehouwer , et al. · 2023

Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples Open

Robin Wijngaard, German Demidov, Luke O’Gorman, Jordi Corominas‐Galbany, Burcu Yaldız , et al. · 2023

SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness Open

Karlijn Bouman, Jan T. Groothuis, Jonne Doorduin, Nens van Alfen, Floris E.A. Udink ten Cate , et al. · 2023

Background: SELENON(SEPN1)-related myopathy (SELENON-RM) is a rare congenital neuromuscular disease characterized by proximal and axial muscle weakness, spinal rigidity, scoliosis and respiratory impairment. No curative treatment options e…

Genome sequencing as a generic diagnostic strategy for rare disease Open

Gaby Schobers, Ronny Derks, Amber den Ouden, Hilde Swinkels, Jeroen van Reeuwijk , et al. · 2023

Background To diagnose the full spectrum of hereditary and congenital diseases, genetic laboratories use many different workflows, ranging from karyotyping to exome sequencing. A single generic high-throughput workflow would greatly increa…

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