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Brunet, T.* ; McWalter, K.* ; Mayerhanser, K.* ; Anbouba, G.M.* ; Armstrong-Javors, A.* ; Bader, I.* ; Baugh, E.* ; Begtrup, A.* ; Bupp, C.P.* ; Callewaert, B.L.* ; Cereda, A.* ; Cousin, M.A.* ; Jimenez, J.C.D.R.* ; Demmer, L.* ; Dsouza, N.R.* ; Fleischer, N.* ; Gavrilova, R.H.* ; Ghate, S.* ; Graf, E. ; Green, A.* ; Green, S.R.* ; Iascone, M.* ; Kdissa, A.* ; Klee, D.* ; Klee, E.W.* ; Lancaster, E.* ; Lindström, K.* ; Mayr, J.A.* ; McEntagart, M.* ; Meeks, N.J.L.* ; Mittag, D.* ; Moore, H.* ; Olsen, A.K.* ; Ortiz, D.* ; Parsons, G.* ; Pena, L.D.M.* ; Person, R.E.* ; Punj, S.* ; Ramos-Rivera, G.A.* ; Sacoto, M.J.G.* ; Bradley Schaefer, G.* ; Schnur, R.E.* ; Scott, T.M.* ; Scott, D.A.* ; Serbinski, C.R.* ; Shashi, V.* ; Siu, V.M.* ; Stadheim, B.F.* ; Sullivan, J.A.* ; Švantnerová, J.* ; Velsher, L.* ; Wargowski, D.S.* ; Wentzensen, I.M.* ; Wieczorek, D.* ; Winkelmann, J. ; Yap, P.* ; Zech, M. ; Zimmermann, M.T.* ; Meitinger, T.* ; Distelmaier, F.* ; Wagner, M.

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder.

Genet. Med. 23, 384–395 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Purpose We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Methods Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. Results We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. Conclusion Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Autism ; Developmental Delay ; Histone Acetylation ; Msl3 ; X-linked; Dosage Compensation; Transcriptional Regulation; Msl Complex; Acetylation; Mutations; Domain; Decay; Mof
ISSN (print) / ISBN 1530-0366
e-ISSN 1098-3600
Journal Genetics in Medicine
Quellenangaben Volume: 23, Issue: , Pages: 384–395 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Baltimore, Md.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Neurogenomics (ING)
Grants Duke University Health System
Progetto GENE (Genomic Analysis Evaluation Network)
Elterninitiative Kinderkrebsklinik e.V. (Dusseldorf)
German Research Foundation/Deutsche Forschungsgemeinschaft