Prenatal Diagnosis of 4p and 4q Subtelomeric Microdeletion in De Novo Ring Chromosome 4

Abstract

Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0) referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH). However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb) and 4q35.2 (2.449 Mb). In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis.

Identification of a novel isolated 4q35.2 microdeletion in a Chinese pediatric patient using chromosomal microarray analysis: a case report and literature review

“…On the other hand, fetal growth restriction was observed in the fetal period (in the studies cases), so it cannot be ruled out that intellectual disability may occur during in childhood and after birth. In addition, another similar study conducted by Akbas et al [ 20 ] demonstrated a case of 2.449Mb terminal 4q35.2 microdeletion in a fetus with growth retardation, also associated with 4p16.3 deletion (size 130 kb without covering the Wolf Hirschhorn critical region). Another related study [ 21 ] elicited a 5.75 Mb interstitial deletion in the 4q35.1q35.2 region in the mother and her two daughters who had no remarkable phenotypic defects.…”

Clinical, cytogenetic, and molecular findings in a patient with ring chromosome 4: case report and literature review

“…Previously, an interstitial deletion of 5.75 Mb has been described in the genomic region 4q35.1-q35.2 between 184,717, 878 and 190,469,337 bp without discernible clinical effects [60]. In other cases, proportional to the size of the loss in 4q35, four genes were in the deletion of 2, 449,000 bp [48], and 19 genes were in the deletion of 5, 090,342 bp [40].…”

“…In our case and six other cases with ring chromosome 4 [3,40,42,44,48,51], array-CGH was used to delimit the loss. However, only in our case and the other four cases [3,42,44,48] has the loss been identified in 4p with an average size of 975,315 bp (range, 130,153-1,710,458 bp), and in this and two other cases [40,48], the loss in 4q has an average size of 3,531, 973 bp (range, 2,449,000-5,090,342 bp) (Fig. 6).…”

“…Diseases associated with CTBP1 include hypotonia, ataxia, developmental delay and tooth enamel defect syndrome [58]. In the other cases studied by array, the number of genes involved in the deletion was according to the size of the loss: six genes in the 130,153 bp deletion [48], 14 genes in the 759,758 bp deletion [42], 16 genes at the deletion of 897,434 bp [44] and 31 genes at the deletion of 1,378,772 bp [3].…”