Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients
Autor: | Seyedeh Sedigheh Abedini, Zohreh Fattahi, Kimia Kahrizi, Maryam Beheshtian, Hossein Najmabadi, Marzieh Mohseni, Sepideh Mehvari, Payman Jamali, Tara Akhtarkhavari, Hans-Hilger Ropers, Vera M. Kalscheuer, Hao Hu, Sanaz Arzhangi, Mahsa Fadaee, Reza Najafipour |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Microcephaly Adolescent Adaptor Protein Complex 4 Consanguinity 030105 genetics & heredity Iran Quadriplegia Corpus Callosum Cohort Studies 03 medical and health sciences Internal medicine Intellectual Disability Intellectual disability Genetics medicine Humans Spasticity Global developmental delay Child Spastic tetraplegia Genetics (clinical) Genetic Association Studies business.industry Brain medicine.disease Phenotype Pedigree 030104 developmental biology Child Preschool Mutation Female medicine.symptom business Ventriculomegaly |
Zdroj: | Clinical Genetics: an international journal of genetics in medicine |
ISSN: | 1399-0004 |
Popis: | 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. |
Databáze: | OpenAIRE |
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