Rad, Aboulfazl;
Bartsch, Oliver;
Bakhtiari, Somayeh;
Zhu, Changlian;
Xu, Yiran;
Monteiro, Fabiola P;
Kok, Fernando;
... Vona, Barbara; + view all
(2024)
Expanding the spectrum of phenotypes for MPDZ: Report of four unrelated families and review of the literature.
Clinical Genetics
, 106
(4)
pp. 413-426.
10.1111/cge.14563.
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Abstract
MPDZ, a gene with diverse functions mediating cell–cell junction interactions, receptor signaling, and binding multivalent scaffold proteins, is associated with a spectrum of clinically heterogeneous phenotypes with biallelic perturbation. Despite its clinical relevance, the mechanistic underpinnings of these variants remain elusive, underscoring the need for extensive case series and functional investigations. In this study, we conducted a systematic review of cases in the literature through two electronic databases following the PRISMA guidelines. We selected nine studies, including 18 patients, with homozygous or compound heterozygous variants in MPDZ and added five patients from four unrelated families with novel MPDZ variants. To evaluate the role of Mpdz on hearing, we analyzed available auditory electrophysiology data from a knockout murine model (Mpdzem1(IMPC)J/em1(IMPC)J) generated by the International Mouse Phenotyping Consortium. Using exome and genome sequencing, we identified three families with compound heterozygous variants, and one family with a homozygous frameshift variant. MPDZ-related disease is clinically heterogenous with hydrocephaly, vision impairment, hearing impairment and cardiovascular disease occurring most frequently. Additionally, we describe two unrelated patients with spasticity, expanding the phenotypic spectrum. Our murine analysis of the Mpdzem1(IMPC)J/em1(IMPC)J allele showed severe hearing impairment. Overall, we expand understanding of MPDZ-related phenotypes and highlight hearing impairment and spasticity among the heterogeneous phenotypes.
| Type: | Article |
|---|---|
| Title: | Expanding the spectrum of phenotypes for MPDZ: Report of four unrelated families and review of the literature |
| Location: | Denmark |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/cge.14563 |
| Publisher version: | https://doi.org/10.1111/cge.14563 |
| Language: | English |
| Additional information: | © 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | hearing loss, hydrocephaly, MPDZ, phenotypic heterogeneity, spasticity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10206895 |
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