Subtelomeric Copy Number Variations: The Importance of 4p/4q Deletions in Patients with Congenital Anomalies and Developmental Disability.
The most prevalent structural variations in the human genome are copy number variations (CNVs), which appear predominantly in the subtelomeric regions. Variable sizes of 4p/4q CNVs have been associated with several different psychiatric findings and developmental disability (DD). We analyzed 105 patients with congenital anomalies (CA) and developmental and/or intellectual disabilities (DD/ID) using MLPA subtelomeric specific kits (P036 /P070) and 4 of them using microarrays. We found abnormal subtelomeric CNVs in 15 patients (14.3%), including 8 patients with subtelomeric deletions at 4p/4q (53.3%). Additional genomic changes were observed at 1p36, 2q37.3, 5p15.3, 5q35.3, 8p23.3, 13q11, 14q32.3, 15q11.2, and Xq28/Yq12. This indicates the prevalence of independent deletions at 4p/4q, involving PIGG, TRIML2, and FRG1. Furthermore, we identified 15 genes with changes in copy number that contribute to neurological development and/or function, among them CRMP1, SORCS2, SLC25A4, and HELT. Our results highlight the association of genes with changes in copy number at 4p and 4q subtelomeric regions and the DD phenotype. Cytogenomic characterization of additional cases with distal deletions should help clarifying the role of subtelomeric CNVs in neurological diseases.
Department of Pathology, Cytogenomics Laboratory, Instituto da Criança, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Gil M
GM
Novo-Filho
Marília M
MM
Montenegro
Évelin A
ÉA
Zanardo
Roberta L
RL
Dutra
Alexandre T
AT
Dias
Flavia B
FB
Piazzon
Taís V M M
TV
Costa
Amom M
AM
Nascimento
Rachel S
RS
Honjo
Chong A
CA
Kim
Leslie D
LD
Kulikowski
D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D016615:Telomere / Q000235:genetics
C000613482:PIGG protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor)