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Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients

Beheshtian, Maryam and Akhtarkhavari, Tara and Mehvari, Sepideh and Mohseni, Marzieh and Fattahi, Zohreh and Abedini, Seyedeh Sedigheh and Najafipour, Reza and Najmabadi, Hossein (2021) Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients. Clinical Genetics, 99 (1). pp. 187-192.

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Abstract

Mutations in adaptor protein complex-4 (AP-4) genes have first been identified in 2009, causing a phenotype termed as AP-4 deficiency syndrome. Since then several patients with overlapping phenotypes, comprised of intellectual disability (ID) and spastic tetraplegia have been reported. To delineate the genotype-phenotype correlation of the AP-4 deficiency syndrome, we add the data from 30 affected individuals from 12 out of 640 Iranian families with ID in whom we detected disease-causing variants in AP-4 complex subunits, using next-generation sequencing. Furthermore, by comparing genotype-phenotype findings of those affected individuals with previously reported patients, we further refine the genotype-phenotype correlation in this syndrome. The most frequent reported clinical findings in the 101 cases consist of ID and/or global developmental delay (97%), speech disorders (92.1%), inability to walk (90.1%), spasticity (77.2%), and microcephaly (75.2%). Spastic tetraplegia has been reported in 72.3% of the investigated patients. The major brain imaging findings are abnormal corpus callosum morphology (63.4%) followed by ventriculomegaly (44.5%). Our result might suggest the AP-4 deficiency syndrome as a major differential diagnostic for unknown hereditary neurodegenerative disorders.

Item Type: Article
Subjects: R Medicine > RH Basic Medical Sciences > RH1001 Biochemistry & Genetics
Divisions: University Portal > vice chancellor > vcr
Depositing User: Mrs Shahrzad Gholami
Date Deposited: 15 Feb 2021 05:45
Last Modified: 15 Feb 2021 05:45
URI: http://eprints.qums.ac.ir/id/eprint/10535

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