Universität zu Köln

Khuller, Katharina, Yigit, Goekhan, Grijalva, Carolina Martinez, Altmueller, Janine, Thiele, Holger, Nurnberg, Peter, Elcioglu, Nursel H., Yeter, Burcu, Hehr, Ute, Stein, Anja, Della Marina, Adela, Koeninger, Angela, Depienne, Christel, Kaiser, Frank J., Wollnik, Bernd ORCID: 0000-0003-2589-0364 and Kuechler, Alma (2021). MFSD2A-associated primary microcephaly-Expanding the clinical and mutational spectrum of this ultra-rare disease. Eur. J. Med. Genet., 64 (10). AMSTERDAM: ELSEVIER. ISSN 1878-0849

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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:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Khuller, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Yigit, Goekhan UNSPECIFIED UNSPECIFIED UNSPECIFIED Grijalva, Carolina Martinez UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Nurnberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Elcioglu, Nursel H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yeter, Burcu UNSPECIFIED UNSPECIFIED UNSPECIFIED Hehr, Ute UNSPECIFIED UNSPECIFIED UNSPECIFIED Stein, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Della Marina, Adela UNSPECIFIED UNSPECIFIED UNSPECIFIED Koeninger, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Depienne, Christel UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaiser, Frank J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wollnik, Bernd UNSPECIFIED orcid.org/0000-0003-2589-0364 UNSPECIFIED Kuechler, Alma UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-596772
DOI:	10.1016/j.ejmg.2021.104310
Journal or Publication Title:	Eur. J. Med. Genet.
Volume:	64
Number:	10
Date:	2021
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1878-0849
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MAJOR FACILITATOR SUPERFAMILY; MFSD2A; TRANSPORTER; BRAIN; SUPPRESSION; RECEPTOR Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59677