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| Skeletal dysplasia v1.166 | IFT52 |
Eleanor Williams changed review comment from: 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.; to: 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. |
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| Skeletal dysplasia v1.166 | IFT52 |
Eleanor Williams commented on gene: IFT52: 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. |
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