In:
Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-4-12)
Abstract:
Phelan-McDermid syndrome (PMS, OMIM# 606232) results from either different rearrangements at the distal region of the long arm of chromosome 22 (22q13.3) or pathogenic sequence variants in the SHANK3 gene. SHANK3 codes for a structural protein that plays a central role in the formation of the postsynaptic terminals and the maintenance of synaptic structures. Clinically, patients with PMS often present with global developmental delay, absent or severely delayed speech, neonatal hypotonia, minor dysmorphic features, and autism spectrum disorders (ASD), among other findings. Here, we describe a cohort of 210 patients with genetically confirmed PMS. We observed multiple variant types, including a significant number of small deletions ( & lt;0.5 Mb, 64/189) and SHANK3 sequence variants (21 cases). We also detected multiple types of rearrangements among microdeletion cases, including a significant number with post-zygotic mosaicism (9.0%, 17/189), ring chromosome 22 (10.6%, 20/189), unbalanced translocations ( de novo or inherited, 6.4%), and additional rearrangements at 22q13 (6.3%, 12/189) as well as other copy number variations in other chromosomes, unrelated to 22q deletions (14.8%, 28/189). We compared the clinical and genetic characteristics among patients with different sizes of deletions and with SHANK3 variants . Our findings suggest that SHANK3 plays an important role in this syndrome but is probably not uniquely responsible for all the spectrum features in PMS. We emphasize that only an adequate combination of different molecular and cytogenetic approaches allows an accurate genetic diagnosis in PMS patients. Thus, a diagnostic algorithm is proposed.
Type of Medium:
Online Resource
ISSN:
1664-8021
DOI:
10.3389/fgene.2022.652454
DOI:
10.3389/fgene.2022.652454.s001
DOI:
10.3389/fgene.2022.652454.s002
DOI:
10.3389/fgene.2022.652454.s003
DOI:
10.3389/fgene.2022.652454.s004
DOI:
10.3389/fgene.2022.652454.s005
DOI:
10.3389/fgene.2022.652454.s006
DOI:
10.3389/fgene.2022.652454.s007
DOI:
10.3389/fgene.2022.652454.s008
DOI:
10.3389/fgene.2022.652454.s009
DOI:
10.3389/fgene.2022.652454.s010
DOI:
10.3389/fgene.2022.652454.s011
DOI:
10.3389/fgene.2022.652454.s012
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606823-0
Permalink