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| Skeletal dysplasia v1.214 | KIAA0753 | Eleanor Williams Classified gene: KIAA0753 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.214 | KIAA0753 | Eleanor Williams Added comment: Comment on list classification: Adding this ciliopathy gene to the skeletal dysplasia panel after consultation with the Genomics England clinical team. The reported phenotypes include skeletal dysplasias. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.214 | KIAA0753 | Eleanor Williams Gene: kiaa0753 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.213 | KIAA0753 |
Eleanor Williams gene: KIAA0753 was added gene: KIAA0753 was added to Skeletal dysplasia. Sources: Other Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA0753 were set to 29138412; 28220259; 26643951 Phenotypes for gene: KIAA0753 were set to ?Orofaciodigital syndrome XV 617127; Joubert syndrome; Short-rib skeletal dysplasia Review for gene: KIAA0753 was set to GREEN Added comment: Provisionally associated with ?Orofaciodigital syndrome XV (617127) in OMIM PMID: 26643951 - Chevrier et al 2016 - 1 case of a newborn female presenting with an oral-facial-digital (OFD) VI syndrome in which they identified two causal heterozygous mutations in the KIAA0753 gene. Both KIAA0753 mutations, one nonsense variant (c.1891A>T; p.Lys631*) and one substitution in Intron 8 (c.1546-3C>A), were confirmed by Sanger sequencing, as well as the maternal heterozygous status for the non-sense variant. PMID: 28220259 - Stephen et al 2017 - 2 siblings with Joubert syndrome associated with growth hormone deficiency but no oral or digital anomalies. Whole exome sequencing of the family identified compound heterozygous mutations in KIAA0753, i.e., a missense mutation (p.Arg257Gly) and an intronic mutation (c.2359-1G>C). PMID: 29138412 - Hammarsjö et al 2017 - report biallelic pathogenic variants in KIAA0753 in four patients from 3 families with short-rib type skeletal dysplasia - ranging from prenatal lethality in one fetus to viability with moderate skeletal dysplasia in three children. 2 families had the same homozygous nonsense variant but are not thought to be related. In the 3rd family the index patient was compound heterogyzous. KIAA0753 is expressed in normal fetal human growth plate and they show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning. In family 1, they also identified an additional homozygous missense variant, c.425 C > T (p.Thr142Met) in SLC13A5 and conclude that the seizures and teeth hypoplasia in P1 and P2 are due to the homozygous SLC13A5 variant. Sources: Other |
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