Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Brunet T

PROVIDER: S-EPMC7862064 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Brunet Theresa T McWalter Kirsty K Mayerhanser Katharina K Anbouba Grace M GM Armstrong-Javors Amy A Bader Ingrid I Baugh Evan E Begtrup Amber A Bupp Caleb P CP Callewaert Bert L BL Cereda Anna A Cousin Margot A MA Del Rey Jimenez Juan C JC Demmer Laurie L Dsouza Nikita R NR Fleischer Nicole N Gavrilova Ralitza H RH Ghate Sumedha S Graf Elisabeth E Green Andrew A Green Sarah R SR Iascone Maria M Kdissa Ameni A Klee Dirk D Klee Eric W EW Lancaster Emily E Lindstrom Kristin K Mayr Johannes A JA McEntagart Meriel M Meeks Naomi J L NJL Mittag Dana D Moore Harrison H Olsen Anne K AK Ortiz Damara D Parsons Gretchen G Pena Loren D M LDM Person Richard E RE Punj Sumit S Ramos-Rivera Gonzalo Alonso GA Sacoto Maria J Guillen MJG Bradley Schaefer G G Schnur Rhonda E RE Scott Tiana M TM Scott Daryl A DA Serbinski Carolyn R CR Shashi Vandana V Siu Victoria M VM Stadheim Barbro Fossøy BF Sullivan Jennifer A JA Švantnerová Jana J Velsher Lea L Wargowski David S DS Wentzensen Ingrid M IM Wieczorek Dagmar D Winkelmann Juliane J Yap Patrick P Zech Michael M Zimmermann Michael T MT Meitinger Thomas T Distelmaier Felix F Wagner Matias M

Genetics in medicine : official journal of the American College of Medical Genetics 20201111 2

<h4>Purpose</h4>We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome).<h4>Methods</h4>Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers.<h4>Results</h4>We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-dele ...[more]

PMID: 33173220

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Dataset Information

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

Purpose

Methods

Results

Conclusion

Publications

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

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