Chromosomal microarray analysis (CMA) detects a large X chromosome deletion including FMR1, FMR2, and IDS in a female patient with mental retardation.
Chromosomal microarray analysis (CMA) by array-based comparative genomic hybridization (CGH) is a new clinical test for the detection of well-characterized genomic disorders caused by chromosomal deletions and duplications that result in gene copy number variation (CNV). This powerful assay detects an abnormality in approximately 7-9% of patients with various clinical phenotypes, including mental retardation. We report here on the results found in a 6-year-old girl with mildly dysmorphic facies, obesity, and marked developmental delay. CMA was requested and showed a heterozygous loss in copy number with clones derived from the genomic region cytogenetically defined as Xq27.3-Xq28. This loss was not cytogenetically visible but was seen on FISH analysis with clones from the region. Further studies confirmed a loss of one copy each of the FMR1, FMR2, and IDS genes (which are mutated in Fragile X syndrome, FRAXE syndrome, and Hunter syndrome, respectively). Skewed X-inactivation has been previously reported in girls with deletions in this region and can lead to a combined Fragile X/Hunter syndrome phenotype in affected females. X-inactivation and iduronate 2-sulfatase (IDS) enzyme activity were therefore examined. X-inactivation was found to be random in the child's peripheral leukocytes, and IDS enzyme activity was approximately half of the normal value. This case demonstrates the utility of CMA both for detecting a submicroscopic chromosomal deletion and for suggesting further testing that could possibly lead to therapeutic options for patients with developmental delay.
Probst
Frank J
FJ
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Roeder
Elizabeth R
ER
Enciso
Victoria B
VB
Ou
Zhishuo
Z
Cooper
M Lance
ML
Eng
Patricia
P
Li
Jiangzhen
J
Gu
Yanghong
Y
Stratton
Robert F
RF
Chinault
A Craig
AC
Shaw
Chad A
CA
Sutton
V Reid
VR
Cheung
Sau Wai
SW
Nelson
David L
DL
D002648:Child; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D015534:Trans-Activators / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics
D051860:Fragile X Messenger Ribonucleoprotein 1; D006023:Glycoproteins; D009687:Nuclear Proteins; D015534:Trans-Activators; C099930:AFF2 protein, human; C497683:FMR1 protein, human; C018322:IDS protein, human