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Neuhofer, C.M.* ; Catarino, C.B.* ; Schmidt, H.* ; Seelos, K.* ; Alhaddad, B. ; Haack, T.B. ; Klopstock, T.*

LINS1-associated neurodevelopmental disorder family with novel mutation expands the phenotypic spectrum.

Neurol. Genet. 6:e500 (2020)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
Objective Clinical, neuroimaging, and genetic characterization of 3 patients with LINS1-associated developmental regression, intellectual disability, dysmorphism, and further neurologic deficits. Methods Three affected brothers from a consanguineous family from Afghanistan, their 2 healthy siblings, and both parents were all assessed in the clinic. General and neurologic examination, expert dysmorphology examination, and 3T brain MRI were performed. Whole-exome sequencing was performed for the 3 affected brothers, followed by Sanger sequencing in all available family members. Results The index patient and his 2 affected brothers presented a complex neurologic syndrome with similar features but marked intrafamilial phenotypical variability, including varying degrees of cognitive impairment, speech impairment, dystonia, abnormal eye movements, and dysmorphic features. All 3 affected brothers are homozygous for a novel, pathogenic frameshift mutation in LINS1, c.1672_1679del, and p.Gly558Profs*22, whereas both parents and healthy siblings are heterozygous for the mutation. No major brain malformations were evident in 3T brain MRI of the affected brothers. Conclusion This consanguineous family with a novel mutation expands the spectrum of LINS1-associated disorder to include developmental regression, oculomotor signs, and dystonia, previously not described in the published 9 cases of this rare disorder. The 3T-MRI data from our 3 patients and review of the neuroimaging data in the literature showed unspecific brain MRI changes. LINS1 protein is a known modulating factor of the Wnt signaling pathway, with important roles in organogenesis including of the cerebral cortex. More research is warranted to disentangle the underlying pathophysiologic mechanisms, leading to cognitive impairment and the complex phenotype of LINS1-associated disorder.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 2376-7839
e-ISSN 2376-7839
Zeitschrift Neurology Genetics
Quellenangaben Band: 6, Heft: 5, Seiten: , Artikelnummer: e500 Supplement: ,
Verlag American Academy of Neurology
Verlagsort Minneapolis, Minn.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)