Table 1.
Clinical and molecular characteristics of MCDs patients with variants in known disease-associated genes
| Patient | Sex | Neuroradiologic findings | FOC | Clinical findings | SNV | CNV |
|---|---|---|---|---|---|---|
| Patients with diagnostic variant in MCDs gene | ||||||
| 39189IMID | M | Heterotopy, nodular Corpus callosum agenesis Asymmetric basal ganglia Reduced volume of white matter |
N | Ataxia DD |
TUBB3: chr16:g.89999057 C>T NM_006086.3:c.136C>T(p.(Arg46Trp)) dn | ND |
| 40133IMID | F | Heterotopy Pachygyria, diffuse Cortical dysplasia Brain stem hypoplasia |
N | Epilepsy Hypotonia DD |
DYNC1H1: chr14:g.102499494 C>T NM_001376.4:c.10172C>T (p.(Pro3391Leu)) dn | ND |
| 39856IMID | M | Pachygyria/agyria Lissencephaly |
N | Epilepsy DD |
DCX: chrX:g.110653437 T>A NM_000555.3:c.433T>A(p.(Tyr145Asn)) dn | ND |
| 40391IMID | F | Simplified gyral pattern Corpus callosum dysgenesis |
MIC | Epilepsy Microsomy Facial dysmorphia Endocrine abnormalities |
ASPM: chr1:g.197071453 C>T NM_018136.4:c.6928C>T(p.(Gln2310*)), chr1:g.197112409 CTA>C NM_018136.4:c.972-973del (p.(Asn324Lysfs*5)) |
ND |
| 40913IMID | M | Heterotopy Corpus callosum hypoplasia Cerebellar hypoplasia |
MIC | Epilepsy DD |
TUBA1A: chr12:g.49579229 C>T NM_001270399.1:c.920C>T (p.(Pro307Leu)) dn | ND |
| 41915IMID | F | Pachygyria, focal Corpus callosum hypoplasia |
N | Spastic tetraplegia Central hypotonia Epilepsy |
EP300: chr22:g.41573716 C>T NM_001429.3:c.6001C> T (p.(Pro2001Ser)) dn | ND |
| Patients with variant of unknown clinical significance in MCDs gene | ||||||
| 39969IMID | F | Polymicrogyria, diffuse | MIC | Spastic tetraparesis DD |
MEF2C: chr5:g.88025139C>T NM_001193347.1:c.890C>T (p.(Ser297Leu)) dn |
ND |
| 1793IMID | F | Agyria/pachygyria (temporal lobes and posterior parts of the brain) Corpus callosum agenesis Ventriculomegaly, Dandy Walker continuum features |
MIC | Epilepsy Optic nerve atrophy DD |
TUBB: chr6:g.30691699 C>T NM_001293212.1:c.920C>T (p.(Pro307Leu)) dn | ND |
| 40628IMID | F | Polymicrogyria, focal | MIC | Epilepsy | RELN: chr7:g.103197603 C>T NM_005045.3:c.5618C>T (p.(Thr1873Ile)), chr7:g.103205779C>T NM_005045.3:c.5156C>T (p.(Ser1719Leu)) | ND |
| 40952IMID | F | Polymicrogyria, focal Heterotopy, subcortical Corpus callosum agenesis Interhemispheric cyst |
N | Epilepsy Blindness, left microphthalmia, coloboma, abnormal retinal pigmentation, palatal pseudocleft |
CSPP1: chr8:g.68049809 C>T NM_024790.6:c.1931C>T (p.(Pro644Leu)), chr8:g.68066291C>G NM_024790.6:c.2146C>G (p.(Arg716Gly)) |
ND |
| 38133IMID | F | Polymicrogyria, diffuse Hemimegalencephaly |
MAC | Epilepsy DD |
PTEN: chr10:g.89692980 A>G NM_000314.4:c.464A>G (p.(Tyr155Cys)) | ND |
| Patients with copy number variation | ||||||
| 40726IMID | F | Pachygyria, diffuse Corpus callosum agenesis Abnormal myelination |
MIC | Epilepsy DD Facial dysmorphia Hypotonia |
ND | chr17:g.(1646091_1670471)_(2497122_2497245)del (hg19, NC_000023.10)17p13.3 del (0.8 Mb) |
| 41983IMID | F | Pachygyria diffuse | MIC | Axial hypotonia/spastic quadriplegia Epilepsy DD |
ND | chr15:g.(22684212_22717733)_(23513803_23597805)del (hg19, NC_000023.10)15q11.1q11.2 del (3.11 Mb) |
| Patients with copy number variation + single-nucleotide variation | ||||||
| 39175IMID | M | Abnormal gyration Hemimegalencephaly |
N | Epilepsy Hemiparesis DD |
TSC1: chr9:g.135779052 C>T NM_000368.4:c.2194C>T (p.(His732Tyr)) | chr16:g.(?_28746493)_(29000911_?)dup (hg19, NC_000016.9)16p11.2 |
| 39785IMID | F | Heterotopy, nodular Corpus callosum agenesis |
N | Epilepsy Ataxia DD Facial dysmorphia |
FLNA: NG_011506.1: chrX:g.153578398 G>A NM_001456.1:c.7333+1G>A | chr11:g.(7160441_7208645)_(7542598_7627534)dup (hg19, NC_000023.10)8p11.21-q11.21 dup (5 Mb) 11p15.4 dup (0.5 Mb) |
| 40689IMID | M | Heterotopy, nodular Corpus callosum hypoplasia Brain stem hypoplasia Cerebellar hypoplasia Abnormal septum pellucidum |
N | Axial hypotonia, limb hypertonia Retinal abnormality Epilepsy DD |
L1CAM: chrX:g.153130043 G>A NM_000425.4:c.3163G>A (p.(Gly1055Arg)) | chr6:g.(169134317_169162581)_(170911237_171115067)del,chr15:g.(20861820_20893918)_(32911229_32942613)del (hg19, NC_000023.10)6q27 del (1.75 Mb) 15q11.2q13.3 del (12 Mb) |
M male, F female, FOC fronto-occipital circumference, N normocephaly, MIC microcephaly, MAC macrocephaly, DD developmental delay, SNV single-nucleotide variation, CNV copy number variation, ND not detected, dn de novo