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A novel AP4M1 mutat...
A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency
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Jameel, Muhammad (author)
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- Klar, Joakim (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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Tariq, Muhammad (author)
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Moawia, Abubakar (author)
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Altaf Malik, Naveed (author)
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Seema Waseem, Syeda (author)
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Abdullah, Uzma (author)
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Naeem Khan, Tahir (author)
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- Raininko, Raili (author)
- Uppsala universitet,Enheten för radiologi
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Baig, Shahid Mahmood (author)
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- Dahl, Niklas (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2014-12-14
- 2014
- English.
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 15, s. 133-
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Abstract
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- BACKGROUND:Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder associated with intellectual disability in one-third of cases. Recent findings support Mendelian inheritance in subgroups of patients with the disease. The purpose of this study was to identify a novel genetic cause of paraplegic CP with intellectual disability in a consanguineous Pakistani family.METHODS:We performed whole-exome sequencing (WES) in two brothers with CP and intellectual disability. Analysis of AP4M1 mRNA was performed using quantitative real-time PCR on total RNA from cultured fibroblasts. The brothers were investigated clinically and by MRI.RESULTS:We identified a novel homozygous AP4M1 mutation c.194_195delAT, p.Y65Ffs*50 in the affected brothers. Quantitative RT-PCR analysis showed markedly reduced AP4M1 mRNA levels suggesting partial non-sense mediated mRNA decay. Several clinical and MRI features were consistent with AP-4 complex deficiency. However, in contrast to previously reported cases with AP4M1 mutations our patients show an aggressive behavior and a relatively late onset of disease.CONCLUSION:This study shows an AP4M1 mutation associated with aggressive behavior in addition to mild dysmorphic features, intellectual disability, spastic paraparesis and reduced head circumference. Our findings expand the clinical spectrum associated with AP-4 complex deficiency and the study illustrates the importance of MRI and WES in the diagnosis of patients with CP and intellectual disability.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Jameel, Muhammad
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Klar, Joakim
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Tariq, Muhammad
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Moawia, Abubakar
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Altaf Malik, Nav ...
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Seema Waseem, Sy ...
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show more...
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Abdullah, Uzma
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Naeem Khan, Tahi ...
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Raininko, Raili
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Baig, Shahid Mah ...
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Dahl, Niklas
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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BMC Medical Gene ...
- By the university
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Uppsala University