Article
Cell Biology
Stojan Peric, Vladana Markovic, Ayse Candayan, Els De Vriendt, Nikola Momcilovic, Andrija Savic, Natasa Dragasevic-Miskovic, Marina Svetel, Zorica Stevic, Ivo Bozovic, Sarlota Mesaros, Jelena Drulovic, Ivana Basta, Igor Petrovic, Olivera Tamas, Milija Mijajlovic, Ivana Novakovic, Dragoslav Sokic, Albena Jordanova
Summary: The study analyzed the genetic causes of HSP in adult Serbian patients and found a high genetic diversity in this population. The findings have important implications for molecular diagnostics and broaden the knowledge on the genetic epidemiology of HSP.
Article
Clinical Neurology
Manuela Wiessner, Reza Maroofian, Meng-Yuan Ni, Andrea Pedroni, Juliane S. Muller, Rolf Stucka, Christian Beetz, Stephanie Efthymiou, Filippo M. Santorelli, Ahmed A. Alfares, Changlian Zhu, Anna Uhrova Meszarosova, Elham Alehabib, Somayeh Bakhtiari, Andreas R. Janecke, Maria Gabriela Otero, Jin Yun Helen Chen, James T. Peterson, Tim M. Strom, Peter De Jonghe, Tine Deconinck, Willem De Ridder, Jonathan De Winter, Rossella Pasquariello, Ivana Ricca, Majid Alfadhel, Bart P. van de Warrenburg, Ruben Portier, Carsten Bergmann, Saghar Ghasemi Firouzabadi, Sheng Chih Jin, Kaya Bilguvar, Sherifa Hamed, Mohammed Abdelhameed, Nourelhoda A. Haridy, Shazia Maqbool, Fatima Rahman, Najwa Anwar, Jenny Carmichael, Alistair Pagnamenta, Nick W. Wood, Frederic Tran Mau-Them, Tobias Haack, Maja Di Rocco, Isabella Ceccherini, Michele Iacomino, Federico Zara, Vincenzo Salpietro, Marcello Scala, Marta Rusmini, Yiran Xu, Yinghong Wang, Yasuhiro Suzuki, Kishin Koh, Haitian Nan, Hiroyuki Ishiura, Shoji Tsuji, Laetitia Lambert, Emmanuelle Schmitt, Elodie Lacaze, Hanna Kuepper, David Dredge, Cara Skraban, Amy Goldstein, Mary J. H. Willis, Katheryn Grand, John M. Graham, Richard A. Lewis, Francisca Millan, Ozgur Duman, Nihal Dundar, Gokhan Uyanik, Ludger Schols, Peter Nuernberg, Gudrun Nuernberg, Andrea Catala Bordes, Pavel Seeman, Martin Kuchar, Hossein Darvish, Adriana Rebelo, Filipa Boucanova, Jean-Jacques Medard, Roman Chrast, Michaela Auer-Grumbach, Fowzan S. Alkuraya, Hanan Shamseldin, Saeed Al Tala, Jamileh Rezazadeh Varaghchi, Maryam Najafi, Selina Deschner, Dieter Glaeser, Wolfgang Huettel, Michael C. Kruer, Erik-Jan Kamsteeg, Yoshihisa Takiyama, Stephan Zuchner, Jonathan Baets, Matthis Synofzik, Rebecca Schuele, Rita Horvath, Henry Houlden, Luca Bartesaghi, Hwei-Jen Lee, Konstantinos Ampatzis, Tyler Mark Pierson, Jan Senderek
Summary: This study identified families with neurological diseases caused by HPDL variants, showing various phenotypes ranging from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia. Experimental evidence suggested a role of HPDL in the nervous system and supported its link to neurological disease.
Article
Clinical Neurology
Lotte van de Venis, Vivian Weerdesteyn, Aletta Konijnenburg, Bart P. C. van de Warrenburg, Alexander C. H. Geurts, Jorik Nonnekes
Summary: This study found an association between increased trunk movements and reduced balance capacity in patients with HSP. The increased trunk movements may partly reflect balance correcting strategies, as ankle strategies and foot placement strategies become impaired and insufficient to restore balance after intrinsic perturbations.
JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Sireesha Murala, Elanagan Nagarajan, Pradeep C. Bollu
Summary: Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders involving the corticospinal tracts, characterized by spasticity and weakness in the lower extremities. Classification is based on inheritance pattern, clinical phenotype, and molecular mechanisms. The most common neuropathological feature is axonal degeneration in the lateral corticospinal tracts.
NEUROLOGICAL SCIENCES
(2021)
Article
Genetics & Heredity
Valeriia A. Kovalskaia, Victoriia V. Zabnenkova, Marina S. Petukhova, Zhanna G. Markova, Vyacheslav Yu. Tabakov, Oxana P. Ryzhkova
Summary: Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) is a rare genetic disease caused by biallelic pathogenic variants in the HACE1 gene. We report a clinical case of a 2-year-old male with previously undescribed HACE1 biallelic deletions as the causative gene. Comprehensive diagnostic approaches are needed for patients initially diagnosed with homozygous mutations in HACE1 to overcome false homozygosity.
Review
Pathology
Grainne Mulkerrin, Marcondes C. Franca, Jasmin Lope, Ee Ling Tan, Peter Bede
Summary: This article reviews the progress of imaging techniques in hereditary spastic paraplegias (HSP). The study highlights the use of various imaging modalities, study design, clinical correlations, and methodological approaches in HSP cohorts. Current limitations include genetically admixed cohorts, small sample sizes, lack of postmortem validation, and limited clinical battery. However, collaborative multicenter initiatives and comprehensive clinical profiling have the potential to overcome these limitations and develop viable clinical applications for HSP imaging.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2022)
Article
Clinical Neurology
Ruizhi Deng, Eva Medico-Salsench, Anita Nikoncuk, Reshmi Ramakrishnan, Kristina Lanko, Nikolas A. Kuhn, Herma C. van der Linde, Sarah Lor-Zade, Fatimah Albuainain, Yuwei Shi, Soheil Yousefi, Ivan Capo, Evita Medici van den Herik, Marjon van Slegtenhorst, Rick van Minkelen, Geert Geeven, Monique T. Mulder, George J. G. Ruijter, Dieter Luetjohann, Edwin H. Jacobs, Henry Houlden, Alistair T. Pagnamenta, Kay Metcalfe, Adam Jackson, Siddharth Banka, Lenika De Simone, Abigail Schwaede, Nancy Kuntz, Timothy Blake Palculict, Safdar Abbas, Muhammad Umair, Mohammed AlMuhaizea, Dilek Colak, Hanan AlQudairy, Maysoon Alsagob, Catarina Pereira, Roberta Trunzo, Vasiliki Karageorgou, Aida M. Bertoli-Avella, Peter Bauer, Arjan Bouman, Lies H. Hoefsloot, Tjakko J. van Ham, Mahmoud Issa, Maha S. Zaki, Joseph G. Gleeson, Rob Willemsen, Namik Kaya, Stefan T. Arold, Reza Maroofian, Leslie E. Sanderson, Tahsin Stefan Barakat
Summary: Hereditary spastic paraplegias (HSP) are rare inherited disorders characterized by lower limb spasticity and muscle weakness. Researchers identified bi-allelic truncating variants in the AMFR gene in HSP-affected individuals, leading to a better understanding of the disease. The absence of AMFR disrupts lipid homeostasis and affects ER morphology, but treatment with statins shows potential therapeutic implications.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Shao-Lun Hsu, Hsueh-Wen Hsueh, Shih-Ying Chen, Yung-Yee Chang, Shennie Tan, Chien-Tai Hong, Yu-Shuen Tsai, Kai-Wei Yu, Hsiu-Mei Wu, Yi-Chu Liao, Bing-Wen Soong, Chaur-Jong Hu, Min-Yu Lan, Yi-Chung Lee
Summary: This study investigated the clinical and genetic features of SPG3A in Taiwan and identified that SPG3A accounts for 4% of HSP cases in Taiwan. The most common mutation found in SPG3A patients was ATL1 p.R416C, with 18 patients typically presenting with a pure form HSP phenotype. Haplotype analysis suggested a shared haplotype in patients carrying the p.R416C allele.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Clinical Neurology
Shao-Lun Hsu, Ying-Hao Chen, Cheng-Ta Chou, Ying-Tsen Chou, Yu-Shuen Tsai, Cheng-Tsung Hsiao, Yi-Chu Liao, Yi-Chung Lee
Summary: The study identified ABCD1 mutations in 4.8% of HSP phenotype cases in Taiwan, highlighting the significance of considering ABCD1 mutations in cases of clinically suspected HSP with unknown genetic causes.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Clinical Neurology
Seyed-Mohammad Fereshtehnejad, Philip A. Saleh, Lais M. Oliveira, Neha Patel, Suvorit Bhowmick, Gerard Saranza, Lorraine Kalia
Summary: This study conducted a systematic review and IPD-level meta-analysis on HSP, finding that SPG7 and SPG11 were the most frequent genotypes in HSP-MD. HSP-MD with SPG7 was associated with later onset, ataxia, extraocular movement disturbances, and seizures, while HSP-MD with SPG11 was associated with consanguinity, parkinsonism, dystonia, peripheral neuropathy, and cognitive dysfunction.
NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Yi-Jun Chen, Zai-Qiang Zhang, Meng-Wen Wang, Yu-Sen Qiu, Ru-Ying Yuan, En-Lin Dong, Zhe Zhao, Hai-Tao Zhou, Ning Wang, Wan-Jin Chen, Xiang Lin
Summary: This study identified a novel ALDH18A1 gene mutation and demonstrated the value of splicing mutation prediction in characterizing disease-related intronic variants. The detected variant led to significantly decreased P5CS concentration in the proband's plasma compared to healthy controls. Furthermore, review of previously reported recessive cases indicated that SPG9B patients in this cohort presented with milder symptoms.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Luis Carlos Tabara, Fatema Al-Salmi, Reza Maroofian, Amna Mohammed Al-Futaisi, Fathiya Al-Murshedi, Joanna Kennedy, Jacob O. Day, Thomas Courtin, Aisha Al-Khayat, Hamid Galedari, Neda Mazaheri, Margherita Protasoni, Mark Johnson, Joseph S. Leslie, Claire G. Salter, Lettie E. Rawlins, James Fasham, Almundher Al-Maawali, Nikol Voutsina, Perrine Charles, Laura Harrold, Boris Keren, Edmund R. S. Kunji, Barbara Vona, Gholamreza Jelodar, Alireza Sedaghat, Gholamreza Shariati, Henry Houlden, Andrew H. Crosby, Julien Prudent, Emma L. Baple
Summary: Hereditary spastic paraplegia (HSP), a genetically diverse neurodegenerative disease, can be classified as pure or complex forms. Biallelic variants in the TMEM63C gene were identified in individuals with HSP and mild intellectual disability. Further analysis showed that TMEM63C plays a role in regulating both endoplasmic reticulum and mitochondrial morphologies.
Article
Medicine, General & Internal
Shao-Lun Hsu, Yi-Jiun Lu, Yu-Shuen Tsai, Hua-Chuan Chao, Jong-Ling Fuh, Yi-Chu Liao, Yi-Chung Lee
Summary: This study identified a SPG15 patient with a novel recessive ZFYVE26 mutation in a Taiwanese HSP cohort. Neuropsychological assessment revealed cognitive deficits in the patient, while brain MRI showed specific abnormalities. The prevalence of SPG15 in Taiwanese HSP patients is approximately 0.5%.
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
(2022)
Article
Neurosciences
Reham Khalaf-Nazzal, James Fasham, Nishanka Ubeyratna, David J. Evans, Joseph S. Leslie, Thomas T. Warner, Fida' Al-Hijawi, Shurouq Alshaer, Wisam Baker, Peter D. Turnpenny, Emma L. Baple, Andrew H. Crosby
Summary: A homozygous frameshift alteration in the PTPN23 gene was identified in a Palestinian family with autosomal recessive complex HSP, highlighting the importance of including PTPN23 gene in global HSP gene testing panels.
Letter
Clinical Neurology
Shao-Lun Hsu, Kang-Yang Jih, Kon-Ping Lin, Yi-Chu Liao, Yi-Chung Lee
Summary: We investigated 98 Taiwanese patients with molecularly unassigned hereditary spastic paraplegia (HSP) and found none of them had the NOTCH2NLC GGC repeat expansion, which is the cause of neuronal intranuclear inclusion disease (NIID). Our findings suggest that the NOTCH2NLC GGC repeat expansion may not contribute to HSP.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Genetics & Heredity
Sibel Aylin Ugur Iseri, Emrah Yucesan, Feyza Nur Tuncer, Mustafa Calik, Yesim Kesim, Gunes Altiokka Uzun, Ugur Ozbek
JOURNAL OF HUMAN GENETICS
(2019)
Article
Multidisciplinary Sciences
Ozkan Ozdemir, Ece Egemen, Sibel Aylin Ugur Iseri, Osman Ugur Sezerman, Nerses Bebek, Betul Baykan, Ugur Ozbek
Article
Hematology
Ilker Karacan, Reyhan Diz Kucukkaya, Fatma Nur Karakus, Seyhun Solakoglu, Aslihan Tolun, Veysel Sabri Hancer, Eda Tahir Turanli
TURKISH JOURNAL OF HEMATOLOGY
(2019)
Article
Genetics & Heredity
Rezan Nehir Mavioglu, Bulent Kara, Gur Akansel, Gokhan Nalbant, Aslihan Tolun
Article
Clinical Neurology
Nihan Hande Akcakaya, Garen Haryanyan, Sevcan Mercan, Nejla Sozer, Asuman Ali, Temel Tombul, Ugur Ozbek, Sibel Aylin Ugur Iseri, Zuhal Yapici
NEUROLOGIA I NEUROCHIRURGIA POLSKA
(2019)
Article
Neurosciences
Sule (Sule) Deveci, Zeliha Matur, Yesim (Yesim) Kesim, Gokce (Gokce) Senturk (Sentuk), Gulcan (Gulcan) Sargin-Kurt, Sibel Aylin Ugur (Ugur), Ali Emre Oge (Oge)
Article
Genetics & Heredity
Sara Mumtaz, Gokhan Nalbant, Esra Yildiz Bolukbasi, Zele Huma, Nafees Ahmad, Aslihan Tolun, Sajid Malik
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2020)
Article
Genetics & Heredity
Qandeel Zahra, Cagla Cakmak, Mine Koprulu, Muhammad Shuaib, Nara Sobreira, Louisa Kalsner, Joselito Sobreira, Maria J. Guillen Sacoto, Sajid Malik, Aslihan Tolun
JOURNAL OF HUMAN GENETICS
(2020)
Article
Genetics & Heredity
Esra Yildiz Bolukbasi, Rana Muhammad Kamran Shabbir, Sajid Malik, Aslihan Tolun
Summary: The study identified a new syndrome in a consanguineous Pakistani family involving various skeletal anomalies. Through gene mapping, a homozygous deletion in MYADML2 was found to be associated with specific features of the disorder, providing insight into the gene's potential role in bone patterning and maturation. Further research is needed to confirm and expand on the phenotype associated with MYADML2 deficiency.
JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Mine Koprulu, Aneeta Kumare, Anisa Bibi, Sajid Malik, Aslihan Tolun
Summary: This study reports a 15.5-year-old Pakistani boy with Fraser syndrome 3, who presents with various characteristic symptoms but no symptoms in other organs. This case expands the phenotypic and mutational spectrum of GRIP1, showing that a homozygous GRIP1 truncating variant can manifest with a less severe phenotype.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Mine Koprulu, Rana Muhammad Kamran Shabbir, Qamar Zaman, Gokhan Nalbant, Sajid Malik, Aslihan Tolun
Summary: This study identified two potentially pathogenic gene mutations in a family with intellectual disabilities, but the clinical manifestations of affected individuals did not fully align with the expected phenotypes for these two genes, highlighting the complexity within the family.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2021)
Article
Genetics & Heredity
Garen Haryanyan, Ozkan Ozdemir, Kemal Tutkavul, Aysin Dervent, Semih Ayta, Cigdem Ozkara, Baris Salman, Emrah Yucesan, Yesim Kesim, Seda Susgun, Ugur Ozbek, Betul Baykan, Sibel A. Ugur Iseri, Nerses Bebek
Summary: Lafora disease is a severe form of progressive myoclonus epilepsy that is inherited in an autosomal recessive manner. It is associated with pathogenic variations in the EPM2A or NHLRC1 genes. The disease typically begins with seizures in adolescence and progresses to dementia, status epilepticus, and death within 10 years. Late-onset and slow progressing forms have also been reported, with some cases showing homozygosity for specific gene variants.
JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Sajid Malik, Gokhan Nalbant, Moqadsa Noreen, Muhammad Afzal, Aslihan Tolun
Summary: Five members of a consanguineous Pakistani kinship were reported to have the most severe familial tetramelic transverse autopod deficiency, along with some common features of autosomal recessive Robinow syndrome-1 (RRS1). Through gene mapping and analysis, a homozygous 8-nucleotide deletion in the ROR2 gene was identified as a potential cause of the severe autopod reduction anomalies in this particular phenotype.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Biochemistry & Molecular Biology
Mine Koprulu, Muhammad Naeem, Gokhan Nalbant, Rana M. Kamran Shabbir, Tariq Mahmood, Zele Huma, Sajid Malik, Aslihan Tolun
Summary: This report describes the first case of pachyonychia congenita to involve all ectodermal derivatives and the first recessive KRT17-related PC, identified in seven members of two consanguineous Pakistani families. The atypical PC presents with a unique combination of symptoms including pachyonychia, plantar keratoderma, alopecia, sparse eyebrows, dental anomalies, acanthosis nigricans of neck, dry skin, palmoplantar hyperhidrosis, recurrent blisters, rough sparse hair, and keratosis pilaris. Exome sequencing revealed a homozygous KRT17 mutation in affected individuals, pointing to a recessive inheritance pattern. Additionally, heterozygous variants in KRT17 have been associated with a different phenotype, PC2, suggesting a need for caution in genetic testing and analysis.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Sevcan Mercan, Nihan Hande Akcakaya, Baris Salman, Zuhal Yapici, Ugur Ozbek, Sibel Aylin Ugur Iseri
Summary: This study aimed to dissect the clinical and genetic features in five distinct IDM cases, and identified biallelic loss of function variants in WDR62 and AP4M1 genes in three families, as well as de novo missense variants in SOX11 and TRIO genes in two families. Underline the importance of using multiple inheritance models in NGS data analysis.