Expansion of the spectrum of TUBB4A-related disorders: a new phenotype associated with a novel mutation in the TUBB4A gene

Neurogenetics - Tập 15 - Trang 107-113 - 2014
Lubov Blumkin1,2,3, Ayelet Halevy4, Dominique Ben-Ami-Raichman5,6, Dvir Dahari7, Ami Haviv7, Cohen Sarit6, Dorit Lev2,8,9, Marjo S. van der Knaap10, Tally Lerman-Sagie1,2,3, Esther Leshinsky-Silver2,6,9
1Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel
2Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel
3Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
4Pediatric Neurology and Development Center, Schneider Children’s Medical Center of Israel, Petach-Tiqva, Israel
5Diagnostic Imaging Department, Neuroradiology Unit, Wolfson Medical Center, Holon, Israel
6Molecular Genetic Laboratory, Wolfson Medical Center, Holon, Israel
7Toldot Genetics Ltd., Tel Aviv, Israel
8Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel
9Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
10Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands

Tóm tắt

Mutations in the TUBB4A gene have been identified so far in two neurodegenerative disorders with extremely different clinical features and course: whispering dysphonia, also known as dystonia type 4 (DYT4), and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). We describe a patient with slowly progressive spastic paraparesis, segmental dystonia, intellectual disability, behavioral problems, and evidence of permanent, incomplete myelination associated with progressive cerebellar atrophy. Whole exome sequencing revealed a novel E410K de novo heterozygous mutation in the TUBB4A gene. The clinical and radiological picture of our patient is different from the classic phenotype; thus, it expands the phenotypic variation of TUBB4A-gene-related disorders.

Tài liệu tham khảo

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