Further defining the critical genes for the 4q21 microdeletion disorder.
4q21 microdeletion syndrome (MIM: 613509) is a new genomic disorder characterized by intellectual disability, absent or severely delayed speech, growth retardation, hypotonia, variable brain malformation, and facial dysmorphism. The critical genes had been proposed based on an overlapping 1.37 Mb genomic region. No further refinement has been done since year 2010. Here, we present three cases with 4q21 deletion identified by clinical chromosomal microarray analysis. One of the cases have a de novo 761 kb deletion which is the smallest deletion ever reported at this locus. It provides an opportunity to further define the critical regions/genes associated with specific features of the 4q21 microdeletion syndrome. The evidence support the notion that PRKG2 and RASGEF1B are critical genes for intellectual disability and speech defect, and the heterogeneous nuclear ribonucleoprotein HNRNPD and HNRNPDL (previously known as HNRPDL) genes are associated with growth retardation and hypotonia. © 2016 Wiley Periodicals, Inc.
Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.|Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, P.R. China.
Xuyun
X
Hu
Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, P.R. China.
Xiaoli
X
Chen
Molecular Genetic Diagnosis Center, Shanghai Key Lab of Birth Defects, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, P.R. China.
Bingbing
B
Wu
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
Irene Mademont
IM
Soler
Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, P.R. China.
Shaoke
S
Chen
Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.|Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, P.R. China.|Departments of Laboratory Medicine and Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Yiping
Y
Shen
D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4; D055028:Comparative Genomic Hybridization; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype
4q21 microdeletion; HNRNPD; HNRNPDL; growth retardation; hypotonia