Skeletal dysplasia
Gene: IFT52
other forms of short-rib dysplasia are listed in Cilliopathies with major skeletal involvement gp of SDs. Only 2 cases reported?; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY, SRTD16 #617102
Publications
Associated with Short-rib thoracic dysplasia 16 with or without polydactyly (#617102) in OMIM.
PMID: 26880018 - Girisha et al. 2016 - 1 case. A child from a consanguineous family who had short stature, narrow thorax, short hands and feet, postaxial polydactyly of hands, pigmentary retinopathy, small teeth and skeletal dysplasia. Whole-exome sequencing revealed a homozygous nonsense variant p.R142* in IFT52. This variant was not found in homozygous state in the 1000Genome project, the Exome Variant Server, the Exome Aggregation Consortium database, CentoMD and exome database of a local NGS service provider. The parents are heterozygous carriers.
PMID: 27466190 - Zhang et al 2016 - 1 case. A non-consanguineous family with two fetuses affected by short-rib polydactyly syndrome (SRPS). Radiographic findings, taken at 20 and 23 weeks of gestation, respectively, were consistent between the two fetuses and showed undermineralized skulls, narrow thoraces with moderately shortened ribs and sharp angulations of some lower thoracic ribs, a flat appearance to the acetabular roofs, reverse campomelia of the humeri, mildly bent femurs, and no polydactyly. In one proband compound heterozygosity for two variants was found - a 1bp deletion leading to a frameshift and premature stop codon and a missense variant (c.878delT, pLeu293AlafsX21 and c.595G > A, p.Ala199Thr). One variant was inherited from each of the parents. The IFT52 mutant cells synthesized a significantly reduced amount of IFT52 protein, leading to reduced synthesis of IFT74, IFT81, IFT88 and ARL13B, other key anterograde complex members. Ciliogenesis was also disrupted in the mutant cells, with a 60% reduction in the presence of cilia on mutant cells and loss of cilia length regulation for the cells with cilia.
PMID: 30242358 - Chen et al. 2018 - 1 case. A child from a consangiuneous family of Hui ethnicity was referred to the clinic with nystagmus and severe visual impairment since infancy also presented with severe growth retardation and mild mental retardation. She had narrow chest with short ribs and micromelic limbs. sandal gap in her right foot and dental dysplasia was also noticed. She was found to have a homozygous variation, IFT52 c.556A>G (p.T186A). This was absent in the two unaffected siblings.
PMID: 31042281 - Dupont et al 2019 - report a family with compound heterogyzous variants (one missense, one causing an inframe mutation that results in less efficient splicing) in IFT52 in two foetuses in which a short rib polydactyly syndrome phenotype is described. One variant is inherited from each of the parents. One fetus also had Tortuous ureters and left pelviectasis. They also report another family in which a fetus with only a renal phenotype and a homozygous variant in IFT52 was identified.
Summary - 3 cases plus a 4th with a milder skeletal phenotype.Created: 16 Jul 2019, 12:10 p.m. | Last Modified: 16 Jul 2019, 12:11 p.m.
Panel Version: 1.166
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: IFT52; Initial rating suggestion: amberCreated: 6 Mar 2019, 11:36 a.m.
Added to this panel as green on the Thoracic dystrophies. Only two cases reported by 2 green expert review.Created: 5 Jun 2017, 1:42 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY, SRTD16 #617102
Publications
Phenotypes for gene: IFT52 were changed from SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY, SRTD16 #617102 to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Publications for gene: IFT52 were set to 26880018; 27466190
Publications for gene: IFT52 were set to 2688018; 27466190
Added phenotypes SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY, SRTD16 #617102 for gene: IFT52 Publications for gene IFT52 were changed from 27466190; 26880018 to 2688018; 27466190
Source NHS GMS was added to IFT52. Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
IFT52 was created by arianna
IFT52 was added to Unexplained skeletal dysplasiapanel. Sources: Other