A microdeletion encompassing PHF21A in an individual with global developmental delay and craniofacial anomalies.
In Potocki-Shaffer syndrome (PSS), the full phenotypic spectrum is manifested when deletions are at least 2.1 Mb in size at 11p11.2. The PSS-associated genes EXT2 and ALX4, together with PHF21A, all map to this region flanked by markers D11S1393 and D11S1319. Being proximal to EXT2 and ALX4, a 1.1 Mb region containing 12 annotated genes had been identified by deletion mapping to explain PSS phenotypes except multiple exostoses and parietal foramina. Here, we report a male patient with partial PSS phenotypes including global developmental delay, craniofacial anomalies, minor limb anomalies, and micropenis. Using microarray, qPCR, RT-qPCR, and Western blot analyses, we refined the candidate gene region, which harbors five genes, by excluding two genes, SLC35C1 and CRY2, which resulted in a corroborating role of PHF21A in developmental delay and craniofacial anomalies. This microdeletion contains the least number of genes at 11p11.2 reported to date. Additionally, we also discuss the phenotypes observed in our patient with respect to those of published cases of microdeletions across the Potocki-Shaffer interval.
Section of Reproductive Endocrinology, Infertility and Genetics, Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.|Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, Georgia.
Jonathan D J
JD
Labonne
West Midlands Regional Genetics Service, Birmingham Women's Hospital, Birmingham, United Kingdom.
Julie
J
Vogt
West Midlands Regional Genetics Service, Birmingham Women's Hospital, Birmingham, United Kingdom.
Lisa
L
Reali
Department of Animal Science, Division of Applied Life Science, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea.
Il-Keun
IK
Kong
Section of Reproductive Endocrinology, Infertility and Genetics, Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.|Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, Georgia.|Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Lawrence C
LC
Layman
Section of Reproductive Endocrinology, Infertility and Genetics, Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.|Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, Georgia.
Hyung-Goo
HG
Kim
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000209:etiology / Q000235:genetics*; D002658:Developmental Disabilities / Q000209:etiology / Q000235:genetics*; D005097:Exostoses, Multiple Hereditary / Q000235:genetics; D005145:Face / Q000002:abnormalities; D005260:Female; D017353:Gene Deletion; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; C490666:MAPK8IP1 protein, human; D008565:Membrane Proteins; C486345:PEX16 protein, human; C492634:PHF21A protein, human; D006655:Histone Deacetylases
11p11.2; ALX4; BHC80; BRAF35; CoREST; EXT2; GTF2I; H3K4me0; H3K4me1; H3K4me2; HDAC1; HDAC2; KDM1A; LSD1; MAPK8IP1; PHF21A; Potocki-Shaffer syndrome; ZMYM2; ZMYM3; ZNF217; craniofacial anomalies; developmental delay; haploinsufficiency; histone demethylase; histone eraser; histone reader; microdeletion; micropenis; positional cloning; repressor; tapering finger; unmethylated histone