Lack of C20orf133 and FLRT3 mutations in 43 patients with Kabuki syndrome in Japan

Molecular karyotyping in 17 patients and mutation screening in 41 patients with Kabuki syndrome

“…Maas et al 14 reported de novo ~250 kb deletion including exon 5 of C20orf133 (MACROD2) in a patient with KS. Direct sequencing for the gene in other 62 patients with KS did not detect mutations 14,15 , but the gene may be one of the causative genes for KS in consideration of its genetic heterogeneity.…”

“…[8][9][10][11][12][13] A study of array-based comparative genomic hybridization (CGH) showed a disruption of C20orf133(MACROD2) gene by ~250 kb deletion on a patient with KS 14 , but the following mutation screening for the gene failed to find pathogenic base change within exons in other 19 patients with KS 14 and in 43 Japanese patients. 15 Another study of array CGH with 0.5 -1.2 Mb resolution reported that 2q37 deletions were detected in two patients with Kabuki-like features but their facial feature were not typical for KS. 16 To date, no concordant specific lesion have been found by whole genome scan with array CGH of bacterial artificial chromosome (BAC) clone with 0.5 -1.5…”

Copy Number Variation in Congenital Heart Defects

“…Therefore, the presence of a CNV in a healthy individual (including a parent) is not adequate to rule out a CNV as pathogenic, nor is the de novo nature of a CNV proof of pathogenicity. Vermeeschs et al [12] illustrate this principle by showing de novo CNVs that were attributed as disease causing, but subsequent analysis identified that the phenotype resulted from point mutations in different genes [12][13][14][15][16]. Finally, when considering the gene content of a CNV, the ACMG warns against using data solely derived from model systems [11].…”

Array-CGH analysis indicates a high prevalence of genomic rearrangements in holoprosencephaly: An updated map of candidate loci

“…Moreover, Kuniba et al recently described the results of a deletion assay for the exon 5 in MACROD2 and a mutation analysis of MACROD2 and FLRT3 among 43 patients with KS in Japan (Kuniba, et al, 2008). They also showed that 2 patients out of 18 presented copy number variations in this region, and concluded that MACROD2 and/or FLRT3 could not be the causative gene in most Japanese KS patients.…”