Table 3 Molecular findings in CNTNAP2
From: Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1
CNTNAP2 | Defect | Array Platform and details of NRXN1/CNTNAP2 deletion | Validation of Array data | Inheritance | Carrier parent | Other non-polymorphic CNVs | NRXN1 sequencing | CNTNAP2 sequencing |
|---|---|---|---|---|---|---|---|---|
C1 | CNTNAP2 c.1175_1176dup; p.D393RfsX51 | Affymetrix 6.0 SNP Array, normal results for CNTNAP2 and NRXN1 | paternal | healthy | chr9:9.337.920-10.207.671 mat dup chr13:19.104.340-19.477.398 mat dup | normal | no 2nd mutation; MLPA normal | |
C2 | CNTNAP2 c.2153G>A, p.W718X | Affymetrix 6.0 SNP Array, normal results for CNTNAP2 and NRXN1 | not known | not known | none | normal | no 2nd mutation; MLPA normal | |
C3 | CNTNAP2 c.1083G>A, splice site (p.V361V) | Affymetrix 500 K SNP Array, normal results for CNTNAP2 and NRXN1 | paternal | healthy | none | normal | no 2nd mutation; MLPA normal | |
C4 | CNTNAP2 c.1083G>A, splice site (p.V361V) | Illumina 317 K SNP Array, normal results for CNTNAP2 and NRXN1 | maternal | healthy | pathogenic frameshift mutation in MEF2C (P7, Zweier et al. 2010) [28] | normal | no 2nd mutation; MLPA normal | |
C5 | CNTNAP2 deletion of exons 2-3 | Affymetrix 6.0 SNP Array chr7:146.079.333-146.194.785 115 kb (69 array marker) | Affymetrix 6.0 SNP Array of the parents | maternal | healthy | none | normal, one silent variant | no 2nd mutation |
C6 | CNTNAP2 deletion of exons 3-4 | Illumina Human 660W-Quad chr7:146.144.267-146.374.539 230 kb (53 array marker) | qPCR as reported previously [32] | maternal | healthy | none | normal | no 2nd mutation |
C7 | CNTNAP2 deletion of exons 21-24 | Agilent 2 × 400 K chr7:147.702.165-148.378.711 677 kb | customized Oligonucleotide array | de novo | healthy | chr7:92.394.428-92.530.356 del chr7:93.464.449-94.430.690 del, both de novo conventional karyotyping: 46,XX,der(4)t(4;10)(q25;q24), der(7)t(4;7)(q25;q32), der(10)inv(10)(p13q24)(7;10)(q32;p13), de novo | normal | no 2nd mutation |
published biallelic defects | 2x CNTNAP2 deletion of exons 2-9, homozygous [26]; 1x CNTNAP2 deletion of exons 5-8 + IVS10-1G>T [26]; 10x CNTNAP2 c.3709delG, homozygous [24, 25] | 2x Affymetrix 500 K/250 K Nsp SNP Array; 1x Affymetrix 6.0 SNP Array [26]; 10x no | parents heterozygous carriers | |||||
published heterozygous defects | 2x translocation disrupting CNTNAP2 [12, 33], 1x inversion disrupting CNTNAP2 [3], 5x CNTNAP2 deletion [1, 7, 21], 4x missense variant in CNTNAP2 [3] | 3x BAC array [7], 1x NimbleGen custom array [21], 220 kb-11 Mb | 2x not reported [7], 4x inherited [3], 2x paternal [1, 21], 2x de novo [3, 7] 2x balanced in parent (translocation) [12, 33] |