MFSD2A-associated primary microcephaly - Expanding the clinical and mutational spectrum of this ultra-rare disease
| Autor: | Janine Altmüller, Nursel Elcioglu, Angela Köninger, Bernd Wollnik, Adela Della Marina, Frank J. Kaiser, Burcu Yeter, Gökhan Yigit, Carolina Martínez Grijalva, Anja Stein, Christel Depienne, Ute Hehr, Holger Thiele, Peter Nürnberg, Katharina Khuller, Alma Kuechler |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Microcephaly Developmental Disabilities Medizin Biology Bioinformatics Blood–brain barrier Compound heterozygosity 03 medical and health sciences Epilepsy 0302 clinical medicine Intellectual disability Genetics medicine Humans Genetics (clinical) 030304 developmental biology 0303 health sciences Symporters Brain Infant General Medicine medicine.disease Phenotype Hypsarrhythmia medicine.anatomical_structure Child Preschool Mutation Female medicine.symptom 030217 neurology & neurosurgery Rare disease |
| Zdroj: | European journal of medical genetics. 64(10) |
| ISSN: | 1878-0849 |
| Popis: | MFSD2A, a member of the major facilitator superfamily (MFS), is a transmembrane transporter responsible for the uptake of specific essential fatty acids through the blood-brain barrier (BBB) to the brain. The transporter is crucial for early embryonic brain development and a major factor in the formation and maintenance of the BBB. Mfsd2a-knockout mice show a leakage of the BBB in early embryonic stages and develop a phenotype characterized by microcephaly, cognitive impairment, and anxiety. So far, homozygous or compound heterozygous MFSD2A mutations in humans have only been reported in 13 different families with a total of 28 affected individuals. The phenotypical spectrum of patients with MFSD2A variants is rather broad but all patients present with microcephaly and severe intellectual disability, absent or limited speech, and walking difficulties. Severely affected patients develop seizures and show brain malformations and have, above all, a profound developmental delay hardly reaching any developmental motor milestones. Here, we report on two unrelated individuals with novel homozygous variants in the MFSD2A gene, presenting with severe primary microcephaly, brain malformations, profound developmental delay, and epilepsy, including hypsarrhythmia. Our findings extend the mutational spectrum of the bi-allelic MFSD2A variants causing autosomal recessive primary microcephaly type 15 and broaden the phenotypic spectrum associated with these pathogenic variants emphasizing the role of MFSD2A in early brain development. |
| Databáze: | OpenAIRE |
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