Khuller, Katharina and Yigit, Goekhan and Grijalva, Carolina Martinez and Altmueller, Janine and Thiele, Holger and Nurnberg, Peter and Elcioglu, Nursel H. and Yeter, Burcu and Hehr, Ute and Stein, Anja and Della Marina, Adela and Koeninger, Angela and Depienne, Christel and Kaiser, Frank J. and Wollnik, Bernd and Kuechler, Alma (2021) MFSD2A-associated primary microcephaly-Expanding the clinical and mutational spectrum of this ultra-rare disease. EUROPEAN JOURNAL OF MEDICAL GENETICS, 64 (10): 104310. ISSN 1769-7212, 1878-0849
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MAJOR FACILITATOR SUPERFAMILY; MFSD2A; TRANSPORTER; BRAIN; SUPPRESSION; RECEPTOR; Microcephaly; Development delay; MFSD2A; Blood-brain barrier |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2022 13:04 |
| Last Modified: | 13 Sep 2022 13:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47266 |
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