A novel combination of biallelic IFT122 variants associated with cranioectodermal dysplasia: A case report.

Published on Apr 1, 2021in Experimental and Therapeutic Medicine1.785
· DOI :10.3892/ETM.2021.9742
Qi Yang5
Estimated H-index: 5
,
Qiang Zhang1
Estimated H-index: 1
+ 5 AuthorsJingsi Luo10
Estimated H-index: 10
Sources
Abstract
Cranioectodermal dysplasia (CED) or Sensenbrenner syndrome is a very rare autosomal-recessive disease that is characterized by craniofacial, skeletal and ectodermal abnormalities. The proteins encoded by six CED-associated genes are members of the intraflagelline transport (IFT) system, which serves an essential role in the assembly, maintenance and function of primary cilia. The current study identified compound novel heterozygous IFT122 (NM_052985.3) variants in a male Chinese infant with CED. The latter variant changes the length of the protein and may result in the partial loss-of-function of IFT122. With the simultaneous presence of frameshift and stop-loss variants, the patient manifested typical CED with fine and sparse hair, macrocephaly, dysmorphic facial features and upper limb phocomelia. A number of unusual phenotypic characteristics were additionally observed and included postaxial polydactyly of both hands and feet. The molecular confirmation of CED in this patient expands the CED-associated variant spectrum of IFT122 in CED, while the manifestation of CED in this patient provides additional clinical information regarding this syndrome. Moreover, the two variants identified in the proband provide a novel perspective into the phenotypes caused by different combinations of variants.
References31
Newest
#1Eric R. Brooks (HHMI: Howard Hughes Medical Institute)H-Index: 5
#2Mohammed Tarek Islam (Kettering University)H-Index: 1
Last. Jennifer A. Zallen (Kettering University)H-Index: 28
view all 4 authors...
Neural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here, we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are flat with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constrict...
3 CitationsSource
#1Joanna Walczak-Sztulpa (Poznan University of Medical Sciences)H-Index: 4
#2Renata Posmyk (UMB: Medical University of Białystok)H-Index: 10
Last. Anna Wasilewska (UMB: Medical University of Białystok)H-Index: 20
view all 10 authors...
BACKGROUND: Sensenbrenner syndrome, which is also known as cranioectodermal dysplasia (CED), is a rare, autosomal recessive ciliary chondrodysplasia characterized by a variety of clinical features including a distinctive craniofacial appearance as well as skeletal, ectodermal, liver and renal anomalies. Progressive renal disease can be life-threatening in this condition. CED is a genetically heterogeneous disorder. Currently, variants in any of six genes (IFT122, WDR35, IFT140, IFT43, IFT52 and ...
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#1Atsuhiko Handa (UIHC: University of Iowa Hospitals and Clinics)H-Index: 6
#2Ulrika Voss (Karolinska University Hospital)H-Index: 3
Last. Gen Nishimura (Saitama University)H-Index: 29
view all 5 authors...
Ciliopathy encompasses a diverse group of autosomal recessive genetic disorders caused by mutations in genes coding for components of the primary cilia. Skeletal ciliopathy forms a subset of ciliopathies characterized by distinctive skeletal changes. Common skeletal ciliopathies include Jeune asphyxiating thoracic dysplasia, Ellis–van Creveld syndrome, Sensenbrenner syndrome, and short-rib polydactyly syndromes. These disorders share common clinical and radiological features. The clinical hallma...
3 CitationsSource
#1Yufei Xu (SJTU: Shanghai Jiao Tong University)H-Index: 7
#2Shouqing Sun (SJTU: Shanghai Jiao Tong University)H-Index: 1
Last. Nan Bao (SJTU: Shanghai Jiao Tong University)H-Index: 1
view all 7 authors...
Abstract Syndromic craniosynostosis is a group of multiple conditions with high heterogeneity, and many rare syndromes still remain to be characterized. To identify and analyze causative genetic variants in nine unrelated probands mainly manifested as syndromic craniosynostosis, we reviewed the relevant medical information of the patients and performed the whole exome sequencing, further verified with Sanger sequencing and parental background. Bioinformatics analysis was used to evaluate the pot...
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#1Wenjuan Zhang (UCLA: University of California, Los Angeles)H-Index: 6
#2S. Paige Taylor (UCLA: University of California, Los Angeles)H-Index: 10
Last. Daniel H. CohnH-Index: 63
view all 13 authors...
Defects in the biosynthesis and/or function of primary cilia cause a spectrum of disorders collectively referred to as ciliopathies. A subset of these disorders is distinguished by profound abnormalities of the skeleton that include a long narrow chest with markedly short ribs, extremely short limbs, and polydactyly. These include the perinatal lethal short-rib polydactyly syndromes (SRPS) and the less severe asphyxiating thoracic dystrophy (ATD), Ellis–van Creveld (EVC) syndrome, and cranioecto...
39 CitationsSource
#1Allan Bayat (Central Manchester University Hospitals NHS Foundation Trust)H-Index: 1
#2Bronwyn KerrH-Index: 31
Last. Ddd StudyH-Index: 13
view all 4 authors...
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#1Bram Prevo (UCSD: University of California, San Diego)H-Index: 11
#2Jonathan M. Scholey (UC Davis: University of California, Davis)H-Index: 78
Last. Erwin J.G. Peterman (VU: VU University Amsterdam)H-Index: 53
view all 3 authors...
Intraflagellar transport (IFT) is a form of motor-dependent cargo transport that is essential for the assembly, maintenance, and length control of cilia, which play critical roles in motility, sensory reception, and signal transduction in virtually all eukaryotic cells. During IFT, anterograde kinesin-2 and retrograde IFT dynein motors drive the bidirectional transport of IFT trains that deliver cargo, for example, axoneme precursors such as tubulins as well as molecules of the signal transducti...
103 CitationsSource
#1Joanna Walczak-Sztulpa (Poznan University of Medical Sciences)H-Index: 4
#2Anna Wawrocka (Poznan University of Medical Sciences)H-Index: 9
Last. Krystyna H. ChrzanowskaH-Index: 32
view all 11 authors...
Sensenbrenner syndrome (cranioectodermal dysplasia, CED) is a very rare autosomal recessive ciliopathy. Cranioectodermal dysplasia is characterized by craniofacial, skeletal, and ectodermal abnormalities. About 50 patients have been described to date. Sensenbrenner syndrome belongs to a group of ciliary chondrodysplasias and is a genetically heterogeneous disorder. Mutations in five genes: IFT122, WDR35, IFT43, WDR19, and IFT52 have been associated with CED. All known genes encode proteins that ...
11 CitationsSource
#1Karina C. Silveira (State University of Campinas)H-Index: 3
#2Carolina Araujo Moreno (State University of Campinas)H-Index: 9
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Since most short-rib polydactyly phenotypes are due to genes involved with biogenesis and maintenance of the primary cilium, this group of skeletal dysplasias was recently designated as ciliopathies with major skeletal involvement. Beemer–Langer syndrome or short-rib polydactyly type IV, was first described in 1983, and has, thus far, remained without a defined molecular basis. The most recent classification of the skeletal dysplasias referred to this phenotype as an as-yet unproven ciliopathy. ...
12 CitationsSource
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#2Anju Shukla (KMC: Kasturba Medical College, Manipal)H-Index: 18
Last. Arndt RolfsH-Index: 55
view all 7 authors...
Intraflagellar transport (IFT) is vital for the functioning of primary cilia. Defects in several components of IFT complexes cause a spectrum of ciliopathies with variable involvement of skeleton, brain, eyes, ectoderm and kidneys. We examined 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. The clinical phenotype of the child shows significant overlap with ...
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