Dulski Jaroslaw, Baker Matthew, Banks Samantha A, Bayat Michael, Bruffaerts Rose, Ortiz Cruz Gabriela, Disserol Caio C, Fisher Kristen S, Jose Jainy N, Kalman Bernadette, Kantarci Orhun H, Maltsev Dmytro, Middleton Catherine, Novotni Gabriela, Plaseska-Karanfilska Dijana, Raskin Salmo, Souza Josiane, Teive Helio A, Wszolek Zbigniew K
From the Department of Neurology (J.D., Z.K.W.), Mayo Clinic, Jacksonville, FL; Division of Neurological and Psychiatric Nursing (J.D.), Faculty of Health Sciences, Medical University of Gdansk; Neurology Department (J.D.), St Adalbert Hospital, Copernicus PL Ltd., Gdansk, Poland; Department of Neuroscience (M. Baker), Mayo Clinic, Jacksonville, FL; Department of Neurology (S.A.B., O.H.K.), Mayo Clinic, Rochester, MN; Department of Neurology (M. Bayat); Centre for Rare Diseases (M. Bayat), Aarhus University Hospital, Aarhus, Denmark; Experimental Neurobiology Unit (R.B.), Department of Biomedical Sciences, University of Antwerp; Department of Neurology, Antwerp University Hospital, Belgium; Center for Research in Genetics and Genomics (CIGEN) (G.O.C.), Autonomous University of Coahuila, México; Universidade Federal do Paraná (C.C.D.), Hospital de Clínicas, Departamento de Medicina Interna, Serviço de Neurologia, Curitiba, Brazil; Department of Pediatrics (K.S.F.), Section of Neurology and Developmental Neuroscience, Baylor College of Medicine (BCM), Houston, TX; Department of Paediatrics (J.N.J.), St. Johns Medical College, Bangalore, Karnataka, India; Office of the Dean (B.K.), University of Pécs, School of Medicine; Molecular Medicine (B.K.), Markusovszky University Teaching Hospital, Szombathely, Hungary; Immunology and Molecular Biology Laboratory of Experimental and Clinical Medicine Institute at the O'Bogomolets National Medical University (D.M.), Kyiv, Ukraine; General Practice (C.M.), Brisbane, Queensland, Australia; Department of Cognitive Neurology and Neurodegenerative Diseases (G.N.), University Clinic of Neurology, Medical Faculty, University "Ss. Cyril and Methodius", Institute for Alzheimer's Disease and Neuroscience-Skopje; Research Center for Genetic Engineering and Biotechnology "Georgi D. Efremov" (D.P.-K.), Macedonian Academy of Sciences and Arts, Skopje, North Macedonia; Postgraduate Program in Child and Adolescent (S.R.), Department of Pediatrics, Federal University of Paraná, Curitiba; School of Medicine (J.S.), Pontificia Universidade Católica do Paraná (PUCPR); Department of Genetics (J.S.), Hospital Infantil Pequeno Príncipe; and Universidade Federal do Paraná (H.A.T.), Hospital de Clínicas, Departamento de Medicina Interna, Serviço de Neurologia, Setor de Distúrbios do Movimento, Curitiba, Brazil.
Neurol Genet. 2024 Sep 13;10(5):e200187. doi: 10.1212/NXG.0000000000200187. eCollection 2024 Oct.
To highlight the worldwide presence of -related disorder (-RD), discuss its penetrance, and provide the first haplotype analysis.
Data on patients worldwide were collected, including demographics, genotype, family history, and clinical status. For haplotype analysis, polymorphisms of short tandem repeats in 3 distinct families with p.Ile794Thr variant were examined.
Nineteen new patients were included, at a mean age of 38.7 years (ranging from 11 to 74 years), from 14 families from the Americas, Asia, Australia, and Europe, including the first from Mexico, North Macedonia, and Ukraine. Fifteen variants were found, including 8 novel. Three patients were compound heterozygotes with disease onset at 1, 4, and 22 years. Patients with heterozygous variants developed symptoms at a mean of 39.0 years (range 8-71 years). Four patients died at a mean of 3.3 years from onset (range 2-5 years). Negative family history was noted in 7 patients. In haplotype analysis, 2 families exhibited shared haplotype encompassing ∼6-Mb region downstream of the while the third family displayed a different haplotype.
-RD has a global prevalence. The reasons for negative family history include de novo variants (as shown by the haplotype analysis), mosaicism, and incomplete penetrance, which are possibly modulated by environmental and genetic factors.
强调[疾病名称]相关疾病（[疾病名称]-RD）在全球的存在情况，讨论其外显率，并提供首次单倍型分析。
收集了全球患者的数据，包括人口统计学、基因型、家族史和临床状况。对于单倍型分析，检查了3个具有p.Ile794Thr变异的不同家族中短串联重复序列的多态性。
纳入了19名新患者，平均年龄38.7岁（范围为11至74岁），来自美洲、亚洲、澳大利亚和欧洲的14个家族，包括首例来自墨西哥、北马其顿和乌克兰的患者。发现了15种变异，其中8种为新变异。3名患者为复合杂合子，发病年龄分别为1岁、4岁和22岁。杂合子[疾病名称]变异患者出现症状的平均年龄为39.0岁（范围8至71岁）。4名患者发病后平均3.3年死亡（范围2至5年）。7名患者有阴性家族史。在单倍型分析中，2个家族表现出共享单倍型，涵盖[基因名称]下游约6兆碱基区域，而第三个家族表现出不同的单倍型。
[疾病名称]-RD具有全球患病率。阴性家族史的原因包括新发变异（如单倍型分析所示）、嵌合体和不完全外显率，这些可能受环境和遗传因素调节。
