Severe microcephalyGene: NCAPD3
Comment on list classification: Additional cases, as well as a more significant pattern of microcephaly, are required before inclusion of NCAPD3 on a diagnostic panel.
Created: 31 Jul 2020, 3:53 p.m. | Last Modified: 31 Jul 2020, 3:53 p.m.
Panel Version: 2.15
Associated with Microcephaly 22 in OMIM and a possible gene for Microcephaly with short stature in G2P.
PMID: 27737959 (2016) - Two unrelated cases. Compound heterozygous variants ([c.1783_1784delG, p.Val595Serfs*34];[c.382+14A>G, p.Ser129Metfs*1]) were detected in a 6-years-5-month-old male with microcephaly (OFC -5.4 SD). The second patient (aged 6-years-11-months-old) was less severely microcephalic (OFC -2.7 SD) but additionally had moderate developmental delay, seizures and lower limb hypertonia, and also harboured a homozygous missense variant in NCAPD3 (c.3458T>G, p.Glu1153Ala).
Functional studies indicated that both variants disrupted condensin-dependent mitotic chromosome integrity, providing supporting evidence for pathogenicity. Biallelic variants in other genes encoding subunits of the two condensin complexes result in a similar phenotype.
Created: 31 Jul 2020, 3:52 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Microcephaly 22, primary, autosomal recessive, 617984
Gene: ncapd3 has been classified as Amber List (Moderate Evidence).
gene: NCAPD3 was added gene: NCAPD3 was added to Severe microcephaly. Sources: Literature Mode of inheritance for gene: NCAPD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NCAPD3 were set to 27737959 Phenotypes for gene: NCAPD3 were set to Microcephaly 22, primary, autosomal recessive, 617984 Review for gene: NCAPD3 was set to AMBER