Article
Neurosciences
Yunping Deng, Hongbing Wang, Marion Joni, Radhika Sekhri, Anton Reiner
Summary: Using behavioral testing and morphological methods, we found that in male heterozygous Q175 mice, striatal neuron abnormalities and behavioral deficits begin to develop between 2 and 6 months of age, reflecting early effects of the HD mutation. While no significant loss of striatal neurons was observed at 18 months, there were signs of reduced expression and dendrite attenuation in certain neuron types as early as 6 months. Additionally, certain types of neurons, such as FoxP2+ arkypallidal GPe neurons and subthalamic nucleus neurons, were lost by 18 months but others, like prototypical PARV+ GPe neurons or dopaminergic nigral neurons, remained unaffected.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Article
Clinical Neurology
Hyungwoo Lee, Kijeong Lee, Young Dae Kim, Hyo Suk Nam, Hye Sun Lee, Sunghee Cho, Ji Hoe Heo
Summary: This retrospective observational study of 350 patients with basal ganglia infarction found that degeneration of the substantia nigra (SN) was associated with functional dependence or death at 3 months post-stroke. The presence of SN degeneration was significantly correlated with worse functional outcomes, indicating its potential as a predictive factor for poor stroke prognosis and a target for therapeutic interventions.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Rong Li, Ting Zou, Xuyang Wang, Hongyu Wang, Xiaofei Hu, Fangfang Xie, Li Meng, Huafu Chen
Summary: Parkinson's disease is a progressive neurodegenerative disease characterized by both motor and non-motor symptoms. Research suggests that as the disease progresses, gray matter atrophy in Parkinson's patients spreads from the basal ganglia to other brain regions, potentially playing a key role in motor and non-motor circuits.
HUMAN BRAIN MAPPING
(2022)
Article
Cell Biology
Zhimei Liu, Masaru Shimura, Li Zhang, Weihua Zhang, Jianing Wang, Minako Ogawa-Tominaga, Junling Wang, Xiaohui Wang, Junlan Lv, Wei Shi, Victor Wei Zhang, Kei Murayama, Fang Fang
Summary: This study reported a rare case of MECR-related mitochondrial disease in a Chinese patient, presenting with childhood-onset dystonia and basal ganglia abnormalities but no optic atrophy. Disease progression was controlled with lipoic acid treatment, and visual impairment was not observed.
Article
Multidisciplinary Sciences
Milvia Alata, Valeria Piazza, Carla Jaramillo-Restrepo, Jose R. Eguibar, Carmen Cortes, Victor H. Hernandez
Summary: In this study, the effects of tubulin beta 4a mutation on the central white matter of taiep rats were identified using second harmonic generation microscopy. Nonlinear emissions from the processes and somata of oligodendrocytes in tubulin beta 4a mutant rats were consistently detected, providing a potential diagnostic tool for neurodegenerative diseases.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Zhengxia Zhong, Xiaoyong Yan, Zhengying Fang, Yijun Dong, Jiaxing Tan, Jingyuan Xie, Linhong Hu, Shibin Zhang, Wei Qin
Summary: This study describes a rare case of adolescent-onset NPHP caused by a novel homozygous INVS mutation. The patient progressed to ESRD at the age of 15 years.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, Research & Experimental
Luke A. Perera, Andrew T. Hattersley, Heather P. Harding, Matthew N. Wakeling, Sarah E. Flanagan, Ibrahim Mohsina, Jamal Raza, Alice Gardham, David Ron, Elisa De Franco
Summary: Mutation in the FICD gene leads to dysfunction of the endoplasmic reticulum, resulting in cell loss and diabetes mellitus. The study suggests that regulating the activity of FICD may provide therapeutic benefits for treating related diseases.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Elior Drori, Shai Berman, Aviv A. Mezer
Summary: We developed a method to identify and quantify gradients of microstructure in the single human brain in vivo, and found robust spatial gradients in the striatum. We also discovered a relationship between striatal structural gradients and cortical hierarchy, as well as abnormal gradients in Parkinson's disease patients, explaining their dopaminergic loss and motor dysfunction.
Article
Endocrinology & Metabolism
Berna Eroglu Filibeli, Gonul Catli, Ilkay Ayranci, Hayrullah Manyas, Ozgur Kirbiyik, Bumin Dundar
Summary: Heterozygous loss-of-function mutations in the glucokinase gene cause MODY 2 characterized by asymptomatic fasting hyperglycemia, while homozygous mutations lead to permanent neonatal diabetes mellitus. A 13-year-old patient diagnosed with diabetes mellitus at age 3 due to a homozygous variant in the GCK gene exemplifies the possibility of homozygous variants in GCK gene presenting with a milder phenotype at a later age.
HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Multidisciplinary Sciences
Avi Fellner, Yael Goldberg, Dorit Lev, Lina Basel-Salmon, Oded Shor, Felix Benninger
Summary: TUBB4A-associated disorder is a rare condition with a wide phenotypic spectrum. Entropy-based analysis and structural clustering revealed a continuum of genotype-phenotype correlation and clear separation of benign and pathogenic variants.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Ilaria Palmieri, Tino Emanuele Poloni, Valentina Medici, Susanna Zucca, Annalisa Davin, Orietta Pansarasa, Mauro Ceroni, Livio Tronconi, Antonio Guaita, Stella Gagliardi, Cristina Cereda
Summary: The study compared two cases of different forms of dementia, highlighting similarities and differences in pathology, genetics, and transcriptomics, emphasizing the important role of transcriptome profiling in understanding the pathogenesis of AD and LBD.
Article
Endocrinology & Metabolism
Jun Mori, Atsushi Umemura, Wataru Satake, Pei-Chieng Cha, Yutaka Suzuki, Kyoko Itoh, Tomohiro Chiyonobu
Summary: This study aims to examine the association between TUBB3 mutation and nonalcoholic steatohepatitis (NASH). An 11-year-old girl was diagnosed with TUBB3 E410K syndrome accompanied by NASH.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Clinical Neurology
Carolina Gorodetsky, Elizabeth Pulcine, Pradeep Krishnan, Jaspal Singh, Mahendranath Moharir, Daune MacGregor, Ishvinder Bhathal, Gabrielle DeVeber, Nomazulu Dlamini
Summary: Mineralizing angiopathy is a unique stroke syndrome in children characterized by basal ganglia infarction and lenticulostriate calcification. Newly reported clinical features include later stroke onset, basal ganglia hemorrhage, and additional non-basal ganglia calcifications. Some children had moderate-to-severe neurological deficits, but there were no symptomatic stroke recurrences during follow-up.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2021)
Article
Clinical Neurology
Kailee Butchereit, Michael Manzini, Helene J. Polatajko, Jean-Pierre Lin, Verity M. McClelland, Hortensia Gimeno
Summary: This study conducted a secondary analysis of video-recorded data from CO-OP therapy sessions for children with HMD to identify and categorize cognitive strategies used for skill acquisition. Strategies included distraction and externally focused attention. Different underlying working mechanisms were postulated for these strategies, with implications for therapeutic management.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2022)
Article
Clinical Neurology
Dalit Cayam-Rand, Ting Guo, Anne Synnes, Vann Chau, Connor Mabbott, Isabel Benavente-Fernandez, Ruth E. Grunau, Steven P. Miller
Summary: In very preterm-born children, neonatal thalamic growth and WMI volume predict school-age thalamic volumes. An interaction between FA and WMI impacts school-age thalamic volume, affecting cognition and motor outcomes.
ANNALS OF NEUROLOGY
(2021)
Article
Genetics & Heredity
Emma K. Baker, Marta Arpone, Minh Bui, Claudine M. Kraan, Ling Ling, David Francis, Mathew F. Hunter, Carolyn Rogers, Michael J. Field, Lorena Santa Maria, Victor Faundes, Bianca Curotto, Paulina Morales, Cesar Trigo, Isabel Salas, Angelica M. Alliende, David J. Amor, David E. Godler
Summary: This study found significant associations between FMR1 methylation levels in blood and buccal epithelial cells and FMR1 mRNA levels and intellectual functioning in males with FXS, with stronger relationships seen using MS-QMA compared to mSB.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Melanie Leffler, Louise Christie, Anna Hackett, Bruce Bennetts, Himanshu Goel, David J. Amor, Greg B. Peters, Michael Field, Tracy Dudding-Byth
Summary: The low copy tandem repeat area at Xq28 is prone to recurrent copy number gains, including the K/L mediated duplications of 300 kb size (herein described as the K/L mediated Xq28 duplication syndrome). We describe five families, including nine males with K/L mediated Xq28 duplications, some with regions of greater copy number variation (CNV). We summarise findings in 25 affected males reported to date.
Article
Biochemistry & Molecular Biology
Miya St John, Olivia van Reyk, David A. Koolen, Bert B. A. de Vries, David J. Amor, Angela T. Morgan
Summary: This study provides a detailed characterization of speech and language impairment in Koolen-de Vries syndrome (KdVS). It defines the medical and neurodevelopmental phenotype in the largest cohort of KdVS individuals to date, highlighting the core features of intellectual disability, eye anomalies, structural brain anomalies, and dental problems. While most individuals with KdVS can speak, some use augmentative and alternative communication methods. The study also reveals relative weaknesses in language, literacy, and social skills, and relative strengths in social competence and coping skills.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
David I. Francis, Zornitza Stark, Ingrid E. Scheffer, Tiong Yang Tan, Krithika Murali, Lyndon Gallacher, David J. Amor, Himanshu Goel, Lilian Downie, Chloe A. Stutterd, Emma I. Krzesinski, Anand Vasudevan, Ralph Oertel, Vida Petrovic, Amber Boys, Vivian Wei, Trent Burgess, Karen Dun, Karen L. Oliver, Anne Baxter, Anna Hackett, Samantha Ayres, Sebastian Lunke, Paul Kalitsis, Meaghan Wall
Summary: This study aimed to compare the diagnostic yield of saliva and blood for pathogenic copy number variants (CNVs). The results showed that saliva microarray testing had increased diagnostic utility over blood testing in individuals with syndromic intellectual disability (ID). Mosaic pathogenic CNVs or aneuploidy were detected in saliva but not in blood.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Dongmao Wang, Paul Trevillian, Stephen May, Peter Diakumis, Yanyan Wang, Deb Colville, Melanie Bahlo, Una Greferath, Erica Fletcher, Barbara Young, Heather G. Mack, Judy Savige
Summary: Scalp-Ear-Nipple syndrome, caused by pathogenic KCTD1 variants, is characterized by scalp defect, prominent ears, and rudimentary breasts. This study found further clinical associations in the eye and kidney.
OPHTHALMIC GENETICS
(2023)
Article
Endocrinology & Metabolism
Courtney R. Green, Roberto Bonelli, Brendan R. E. Ansell, Simone Tzaridis, Michal K. Handzlik, Grace H. McGregor, Barbara Hart, Jennifer Trombley, Mary M. Reilly, Paul S. Bernstein, Catherine Egan, Marcus Fruttiger, Martina Wallace, Melanie Bahlo, Martin Friedlander, Christian M. Metallo, Marin L. Gantner
Summary: Metabolomic analysis of MacTel, HSAN1, and dual diagnosed patients revealed metabolic distinctions in amino acid and sphingolipid metabolism. MacTel patients exhibited alterations in amino acids resembling diabetes, as well as changes in sphingolipid levels. HSAN1 patients showed abnormal sphingolipid metabolism compared to controls. These findings have implications for further research and therapeutic approaches for these neurodegenerative diseases.
MOLECULAR METABOLISM
(2023)
Article
Multidisciplinary Sciences
Lyndal Henden, Liam G. Fearnley, Natalie Grima, Emily P. McCann, Carol Dobson-Stone, Lauren Fitzpatrick, Kathryn Friend, Lynne Hobson, Sandrine Chan Moi Fat, Dominic B. Rowe, Susan D'Silva, John B. Kwok, Glenda M. Halliday, Matthew C. Kiernan, Srestha Mazumder, Hannah C. Timmins, Margaret Zoing, Roger Pamphlett, Lorel Adams, Melanie Bahlo, Ian P. Blair, Kelly L. Williams
Summary: In this study, we analyzed whole-genome sequencing data from 608 patients with sporadic ALS, 68 patients with sporadic FTD, and 4703 matched controls using three tools. We found that 17.6% of clinically diagnosed ALS and FTD cases had expanded STR alleles reported to be pathogenic or intermediate for other neurodegenerative diseases, providing evidence for their contribution to the development of these diseases. We also identified multiple disease-relevant STR expansions associated with neurodegenerative diseases, highlighting the clinical and pathological pleiotropy of neurodegenerative disease genes and their importance in ALS and FTD.
Article
Dermatology
Mitchell S. Stark, Richard A. Sturm, Yan Pan, Darren J. Smit, Varsha Kommajosyula, Katie J. Lee, Kasturee Jagirdar, Catriona McLean, David L. Duffy, H. Peter Soyer, Victoria J. Mar
Summary: This study performed a rare-variant allele analysis, identifying some genes associated with nodular melanoma (NM), including PTCH1, ARID2, and GHR. Rare variants in the SMO gene, which interacts with PTCH1, were also found, suggesting a potential contribution of the Hedgehog pathway to NM risk.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Article
Clinical Neurology
Renee Smyth, Susan M. Reid, Kate Paton, Angela T. Guzys, Claire E. Wakefield, David J. Amor
Summary: The aim of this study was to understand parents' beliefs about the causes of cerebral palsy (CP) and the emotions related to those beliefs. A survey was conducted on 226 parents of children with CP aged 1 to 18 years. The majority of participants expressed the importance of understanding the causes of CP, but there was also uncertainty about the causes. The most commonly endorsed causal factors were intrapartum hypoxia, brain damage, and preterm birth, and parents often experienced feelings of anger, sadness, guilt, and confusion.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2023)
Article
Genetics & Heredity
Linda M. Reis, David J. Amor, Raad A. Haddad, Catherine B. Nowak, Kim M. Keppler-Noreuil, Smith Ann Chisholm, Elena V. Semina
Summary: Axenfeld-Rieger anomaly is an ocular disorder associated with other systemic abnormalities. This study identified pathogenic variants in nine families affecting five different genes/regions. USP9X and JAG1 were the most commonly mutated genes associated with the disorder. Variants in CDK13, BCOR, and an X chromosome deletion were also found to be linked with Axenfeld-Rieger syndrome.
Review
Biochemistry & Molecular Biology
Haloom Rafehi, Mark F. Bennett, Melanie Bahlo
Summary: Hereditary cerebellar ataxias are a group of progressive neurological disorders caused by repeat expansions. Significant advances have been made in detecting short tandem repeats (STRs) and repeat expansions using whole-genome sequencing data. Established repeat expansion detection pipelines have become a feasible and practical alternative to molecular testing methods, leading to the discovery of many new pathogenic repeat expansions.
EMERGING TOPICS IN LIFE SCIENCES
(2023)
Article
Endocrinology & Metabolism
Roberto Bonelli, Sasha M. Woods, Sarah Lockwood, Paul N. Bishop, Kamron N. Khan, Melanie Bahlo, Brendan R. E. Ansell, Marcus Fruttiger
Summary: The primate retina has specialized regional functions, with the macula being specialized for high acuity vision. Different regions in the retina have different susceptibility to diseases, with the macula being primarily affected.
Article
Biology
Daniel Frank, Maria Bergamasco, Michael J. Mlodzianoski, Andrew Kueh, Ellen Tsui, Cathrine Hall, Georgios Kastrappis, Anne Kathrin Voss, Catriona McLean, Maree Faux, Kelly L. Rogers, Bang Tran, Elizabeth Vincan, David Komander, Grant Dewson, Hoanh Tran
Summary: Mutation in ZRANB1 gene has been found to be associated with various congenital disorders, including reduced brain size. These mutations affect the regulation of neurite growth and result in reduced neuronal and glial cell densities in the brain, as well as motor deficits.
Article
Dermatology
Sasha Hall, Christopher Y. Chew, Tom Kovitwanichkanont, Ken Hiu-Kan Ip, Jennifer Cahill, Alexander Gin, Catriona A. Mclean, Douglas Gin
AUSTRALASIAN JOURNAL OF DERMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Kevin T. Eade, Brendan Robert E. Ansell, Sarah Giles, Regis Fallon, Sarah Harkins-Perry, Takayuki Nagasaki, Simone Tzaridis, Martina Wallace, Elizabeth A. Mills, Samaneh Farashi, Alec Johnson, Lydia Sauer, Barbara Hart, M. Elena Diaz-Rubio, Melanie Bahlo, Christian Metallo, Rando Allikmets, Marin L. Gantner, Paul S. Bernstein, Martin Friedlander
Summary: Patient-derived iPSCs are a powerful tool for studying disease mechanisms, with MacTel iRPE cells showing reduced serine levels and dysregulation of central carbon metabolism. Mitochondrial dysfunction in these cells may represent an alternative disease mechanism beyond the known serine/sphingolipid pathway.
JOURNAL OF CLINICAL INVESTIGATION
(2023)