PMC9343796_01
PMC9343796_02
Pictures of the proband showing mild dysmorphic features. In both pictures, the proband is slightly tilting her head up; panel (A): an epicanthal fold is noted on the right. On the left, mild microphthalmos is noted. Her ears are standard set with posterior rotation; panel (B): her left ear lobe is notched. The proband has a thin upper lip.
fgene-13-906077-g001.jpg
PMC9343796_02_fgene-13-906077-g001.jpg
F1
Following her most recent early intervention evaluation, she qualified for feeding, speech, physical, occupational therapies, and special instruction (Figures 1A,B).
Cytogenetic and genomic characterization of the sSMC. Panel (A): female karyotype with a small supernumerary marker chromosome identified by G-banding from amniotic fluid; banding resolution: 400-band-level; panel (B): SNP-based microarray results showing 31.34 Mb gain in the distal end of chromosome 13q: arr [GRCh37] 13q31.1q34 (83,666,539_115,010,330)x2~4; probe targets: 2,696,550; human genome build (hg19); panel (C): metaphase and interphase FISH results using probes mapping to 13q14 (D13S319), 13q34 (LAMP1), and chr 13 centromere. The final karyotype is: 47,XX,+mar[28]/46,XX[2]. nuc ish (D13S319x2,LAMP1x4)[122/300]. ish der (13) (D13S319,LAMP1++) (CEP13-); panel (D): chromosome 13 ideograms showing representative normal and marker chromosome 13 in the patient. The long form description of the marker chromosome cell line as per ISCN 2020 is as follows: 47,XX,+dup (13) (qter- > q31.1::q31.1- > q33- > neo- > q33- > qter).
fgene-13-906077-g002.jpg
PMC9343796_02_fgene-13-906077-g002.jpg
F2
Cytogenetic analysis from an amniotic fluid sample showed a mosaic karyotype with a small supernumerary marker chromosome (sSMC) (Figure 2A). SNP probes from the microarray analysis showed four genotypes in the 13q gain, including either 0:4 (AAAA and BBBB) or 1:3 (AAAB and ABBB) genotype ratios for A and B alleles and the absence of 2:2 genotype ratio (AABB) (Figure 2B), which indicates that SNPs on both arms of the duplicated sSMC are identical and they are originated from the same chromosome fragment. Additionally, metaphase FISH testing using the centromeric CEP13 probe failed to hybridize on the sSMC suggesting the presence of a neocentromere (Figure 2C). The marker chromosome was submetacentric in appearance with a primary constriction suggesting the presence of the neocentromere most likely at chromosomal band 13q33 (Figure 2D).