Title |
Identification of a novel genetic locus underlying tremor and dystonia
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Published in |
Human Genomics, November 2017
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DOI | 10.1186/s40246-017-0123-5 |
Pubmed ID | |
Authors |
Dorota Monies, Hussam Abou Al-Shaar, Ewa A. Goljan, Banan Al-Younes, Muna Monther Abdullah Al-Breacan, Maher Mohammed Al-Saif, Salma M. Wakil, Brian F. Meyer, Khalid S. A. Khabar, Saeed Bohlega |
Abstract |
Five affected individuals with syndromic tremulous dystonia, spasticity, and white matter disease from a consanguineous extended family covering a period of over 24 years are presented. A positional cloning approach utilizing genome-wide linkage, homozygozity mapping and whole exome sequencing was used for genetic characterization. The impact of a calmodulin-binding transcription activator 2, (CAMTA2) isoform 2, hypomorphic mutation on mRNA and protein abundance was studied using fluorescent reporter expression cassettes. Human brain sub-region cDNA libraries were used to study the expression pattern of CAMTA2 transcript variants. Linkage analysis and homozygozity mapping localized the disease allele to a 2.1 Mb interval on chromosome 17 with a LOD score of 4.58. Whole exome sequencing identified a G>A change in the transcript variant 2 5'UTR of CAMTA2 that was only 6 bases upstream of the translation start site (c.-6G > A) (NM_001171166.1) and segregated with disease in an autosomal recessive manner. Transfection of wild type and mutant 5'UTR-linked fluorescent reporters showed no impact upon mRNA levels but a significant reduction in the protein fluorescent activity implying translation inhibition. Mutation of CAMTA2 resulting in post-transcriptional inhibition of its own gene activity likely underlies a novel syndromic tremulous dystonia. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Saudi Arabia | 102 | 38% |
United Arab Emirates | 5 | 2% |
United States | 3 | 1% |
United Kingdom | 2 | <1% |
Estonia | 1 | <1% |
Kuwait | 1 | <1% |
Mexico | 1 | <1% |
North Macedonia | 1 | <1% |
Iraq | 1 | <1% |
Other | 0 | 0% |
Unknown | 151 | 56% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 249 | 93% |
Practitioners (doctors, other healthcare professionals) | 15 | 6% |
Scientists | 2 | <1% |
Science communicators (journalists, bloggers, editors) | 2 | <1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 26 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 6 | 23% |
Professor > Associate Professor | 3 | 12% |
Student > Doctoral Student | 2 | 8% |
Student > Master | 2 | 8% |
Student > Bachelor | 1 | 4% |
Other | 4 | 15% |
Unknown | 8 | 31% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 5 | 19% |
Medicine and Dentistry | 3 | 12% |
Arts and Humanities | 2 | 8% |
Agricultural and Biological Sciences | 2 | 8% |
Engineering | 2 | 8% |
Other | 3 | 12% |
Unknown | 9 | 35% |