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| Limb disorders v1.58 | NCAPG2 | Eleanor Williams Classified gene: NCAPG2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.58 | NCAPG2 | Eleanor Williams Added comment: Comment on list classification: 2 cases. Zebra fish model does not show limb phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.58 | NCAPG2 | Eleanor Williams Gene: ncapg2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.37 | NCAPG2 | Eleanor Williams Phenotypes for gene: NCAPG2 were changed from to Khan-Khan-Katsanis syndrome, 618460 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.36 | NCAPG2 | Eleanor Williams Publications for gene: NCAPG2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.35 | NCAPG2 |
Eleanor Williams changed review comment from: Associated with Khan-Khan-Katsanis syndrome (#618460) in OMIM. PMID: 30609410 - Khan et al. 2019 - 2 unrelated cases with homozygous or compound heterozygous variants in NCAPG2. Family 1 - female with bilateral postaxial polydactyly on the feet, moderate intellectual disability, ocular anomalies, sensorineural hearing impairment, sleep apnea, and a short stature. Renal anomalies were also observed although these resolved over time. She was found to have compound-heterozygous missense NCAPG2 mutations, c.1825A>G (p.Lys609Glu) and c.2078C>T (p.Thr693Met); three healthy siblings are either wild-type (WT) or heterozygous for the mutations (mut). Family 2 - proband was a twin with multiple congenital anomalies at birth; these included microcephaly, facial dysmorphisms, digit abnormalities (postaxial absent toes and clinodactyly of the 5th finger), ocular phenotypes (Peters anomaly, bilateral glaucoma, and buphthalmos of the left eye), contractures, neonatal hypertonia, and a sacral dimple. A homozygous missense variant was found in the proband c.2548A>C [p.Thr850Pro]. Both parents are heterozygous for this variant. Functional studies with skin fibroblasts from the proband in family 1, showed abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells. In a ncapg2 zebrafish model, morphants displayed clinically relevant phenotypes, such as renal anomalies, microcephaly, and concomitant increases in apoptosis and altered mitotic progression. These could be rescued by wild-type but not mutant human NCAPG2 mRNA and were recapitulated in CRISPR-Cas9 F0 mutants.; to: Associated with Khan-Khan-Katsanis syndrome (#618460) in OMIM. PMID: 30609410 - Khan et al. 2019 - 2 unrelated cases with homozygous or compound heterozygous variants in NCAPG2. Family 1 - female with bilateral postaxial polydactyly on the feet, moderate intellectual disability, ocular anomalies, sensorineural hearing impairment, sleep apnea, and a short stature. Hydronephrosiss was also observed although this improved over time. She was found to have compound-heterozygous missense NCAPG2 mutations, c.1825A>G (p.Lys609Glu) and c.2078C>T (p.Thr693Met); three healthy siblings are either wild-type (WT) or heterozygous for the mutations (mut). Also of note was a heterozygous NPHP1 deletion, a common contributor to nephronophthisis. Family 2 - proband was a twin with multiple congenital anomalies at birth; these included microcephaly, facial dysmorphisms, digit abnormalities (postaxial absent toes and clinodactyly of the 5th finger), ocular phenotypes (Peters anomaly, bilateral glaucoma, and buphthalmos of the left eye), contractures, neonatal hypertonia, and a sacral dimple. A homozygous missense variant was found in the proband c.2548A>C [p.Thr850Pro]. Both parents are heterozygous for this variant. Functional studies with skin fibroblasts from the proband in family 1, showed abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells. In a ncapg2 zebrafish model, morphants displayed clinically relevant phenotypes, such as renal anomalies, microcephaly, and concomitant increases in apoptosis and altered mitotic progression. These could be rescued by wild-type but not mutant human NCAPG2 mRNA and were recapitulated in CRISPR-Cas9 F0 mutants. |
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| Limb disorders v1.35 | NCAPG2 |
Eleanor Williams commented on gene: NCAPG2: Associated with Khan-Khan-Katsanis syndrome (#618460) in OMIM. PMID: 30609410 - Khan et al. 2019 - 2 unrelated cases with homozygous or compound heterozygous variants in NCAPG2. Family 1 - female with bilateral postaxial polydactyly on the feet, moderate intellectual disability, ocular anomalies, sensorineural hearing impairment, sleep apnea, and a short stature. Renal anomalies were also observed although these resolved over time. She was found to have compound-heterozygous missense NCAPG2 mutations, c.1825A>G (p.Lys609Glu) and c.2078C>T (p.Thr693Met); three healthy siblings are either wild-type (WT) or heterozygous for the mutations (mut). Family 2 - proband was a twin with multiple congenital anomalies at birth; these included microcephaly, facial dysmorphisms, digit abnormalities (postaxial absent toes and clinodactyly of the 5th finger), ocular phenotypes (Peters anomaly, bilateral glaucoma, and buphthalmos of the left eye), contractures, neonatal hypertonia, and a sacral dimple. A homozygous missense variant was found in the proband c.2548A>C [p.Thr850Pro]. Both parents are heterozygous for this variant. Functional studies with skin fibroblasts from the proband in family 1, showed abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells. In a ncapg2 zebrafish model, morphants displayed clinically relevant phenotypes, such as renal anomalies, microcephaly, and concomitant increases in apoptosis and altered mitotic progression. These could be rescued by wild-type but not mutant human NCAPG2 mRNA and were recapitulated in CRISPR-Cas9 F0 mutants. |
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| Limb disorders v1.24 | NCAPG2 | Andrew Wilkie reviewed gene: NCAPG2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.16 | NCAPG2 |
Eleanor Williams gene: NCAPG2 was added gene: NCAPG2 was added to Limb disorders. Sources: Expert list Mode of inheritance for gene: NCAPG2 was set to BIALLELIC, autosomal or pseudoautosomal Review for gene: NCAPG2 was set to AMBER Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust Sources: Expert list |
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