Clinical assessment of five patients with BRWD3 mutation at Xq21.1 gives further evidence for mild to moderate intellectual disability and macrocephaly.
Truncating mutations of the BRWD3 gene have been reported in two distinct families with in total four patients so far. By using array-CGH, we detected a 74 Kb de novo deletion encompassing exons 11 through 41 of BRWD3 at Xq21.1 in a 20 year old boy presenting with syndromic intellectual disability. In addition, by using exome sequencing, we ascertained a family with a BRWD3 nonsense mutation, p.Tyr1131*, in four males with intellectual disability. We compared the clinical presentation of these five patients to that of the four patients already described in the literature for further delineation of the clinical spectrum in BRWD3-related intellectual disability. The main symptoms are mild to moderate intellectual disability (n = 9/9) with speech delay (n = 8/8), behavioral disturbances (n = 7/8), macrocephaly (n = 7/9), dysmorphic facial features (n = 9/9) including prominent forehead, pointed chin, deep-set eyes, abnormal ears, and broad hands and feet (n = 6/6), and skeletal symptoms (n = 7/7) like pes planus, scoliosis, kyphosis and cubitus valgus.
Department of Genetics, Rouen University Hospital, Rouen, France.
Sarah
S
Grotto
Department of Genetics, Rouen University Hospital, Rouen, France.
Valérie
V
Drouin-Garraud
Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Department of Pediatrics, University of Tartu, Tartu, Estonia.
Katrin
K
Ounap
Department of Pediatrics, University of Tartu, Tartu, Estonia; Department of Pediatrics, The Children's Hospital at Westmead, Sydney Children Hospital Network, Sydney, Australia.
Helen
H
Puusepp-Benazzouz
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Janneke
J
Schuurs-Hoeijmakers
Department of Cytogenetics, EFS Normandie, Bois-Guillaume, France.
Nathalie
N
Le Meur
Department of Cytogenetics and Reproductive Biology, Rouen University Hospital, Rouen, France.
Pascal
P
Chambon
Department of Genetics, Rouen University Hospital, Rouen, France.
Séverine
S
Fehrenbach
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
Hans
H
van Bokhoven
Department of Genetics, Rouen University Hospital, Rouen, France; Inserm U1079, Rouen, France; Normandie University, IRIB, Rouen, France.
Thierry
T
Frébourg
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
Arjan P M
AP
de Brouwer
Department of Genetics, Rouen University Hospital, Rouen, France; Inserm U1079, Rouen, France; Normandie University, IRIB, Rouen, France. Electronic address: Pascale.Saugier-Veber@chu-rouen.fr.
Pascale
P
Saugier-Veber
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D041321:Chromosomes, Human, X; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D058627:Megalencephaly / Q000235:genetics*; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D000092468:Bromodomain Containing Proteins
D018389:Codon, Nonsense; D014157:Transcription Factors; C502037:BRWD3 protein, human; D000092468:Bromodomain Containing Proteins
BRWD3; Intellectual disability; Macrocephaly; Xq21.1 deletion