A rare mutant of OFD1 gene responsible for Joubert syndrome with significant phenotype variation

Zhang, Yang-Wei; Qu, Haibo; Long, Ning; Leng, Xiangyou; Yang, Yuan

doi:10.1007/s00438-020-01726-1

Cited by 10 publications

(12 citation statements)

References 17 publications

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“…Laterality defects, such as situs inversus, frequently accompanying cardiac malformations and sometimes complicating other ciliopathies, are also rare in JS. This phenotype has been reported associated with pathogenic variants in CC2D2A, CEP290, OFD1 , and ZFN423 (Bachmann‐Gagescu, Dempsey, et al, 2015; Chaki et al, 2012; Parisi, 2009; Zhang, Qu, et al, 2021).…”

Section: System‐by‐system Review Of Genotype–phenotype Correlationmentioning

confidence: 82%

“…Migration defects described in JS patients include cortical, midbrain, and cervicomedullary heterotopias, polymicrogyria, fronto‐temporal pachigyria, and macrogyria, and have been variably reported in patients carrying pathogenic variants in AHI1, CC2D2A, CSSP1, KIAA0586, OFD1, PIBF1, RPGRIP1L, TCTN1 , and SUFU (Ben‐Salem et al, 2014; De Mori et al, 2017; Dixon‐Salazar et al, 2004; Field et al, 2012; Kroes et al, 2016; Poretti et al, 2017; Shen et al, 2020; Tuz et al, 2014; Zhang et al, 2021; Zhang, Sun, Xu, Che, & Liu, 2021).…”

Section: System‐by‐system Review Of Genotype–phenotype Correlationmentioning

confidence: 99%

“…The NIH cohort, where polydactyly was present in 13 out of 99 JS individuals (13%), substantially confirmed the significant positive correlation between polydactyly and CPLANE1 (Vilboux, Doherty, et al, 2017). Besides this association, polydactyly (mainly postaxial) has been described in several reports in association with the vast majority of JS known genes, including biallelic missense variants in SUFU (Bachmann‐Gagescu, Dempsey, et al, 2015; Bachmann‐Gagescu, Phelps, et al, 2015; Brancati et al, 2009; De Mori et al, 2017; Epting et al, 2020; Hardee et al, 2017; Kar et al, 2018; Kroes et al, 2016; Lambacher et al, 2016; Latour et al, 2020; Lee, Silhavy, Lee, et al, 2012; Powell et al, 2020; Radha Rama Devi et al, 2020; Shaheen et al, 2019; Stephen et al, 2017; Thomas et al, 2014; Van De Weghe et al, 2021; Zhang et al, 2017; Zhang, Qu, et al, 2021; Zhongling, Guoming, Yanhui, & Xiaoru, 2021).…”

Section: System‐by‐system Review Of Genotype–phenotype Correlationmentioning

confidence: 99%

“…Thus, no cardiac screening is recommended for JS patients. Yet, although the incidence of heart defects in JS is small, these have been occasionally reported in patients harboring mutations in several genes, including some prevalent ones such as AHI1, CEP290, CPLANE1, KIAA0586 , and MKS1 (Bader et al, 2016; Fraser & Davey, 2019; Parisi, 2009; Parisi et al, 2006; Zhang, Qu, et al, 2021). In particular, it is of interest the report of a few CEP290 mutated cases presenting with heart defects, mainly atrio‐ventricular septal defect (Alharbi et al, 2018; Bachmann‐Gagescu, Dempsey, et al, 2015; Karp, Grosse‐Wortmann, & Bowdin, 2012; Trevino et al, 2020).…”

Section: System‐by‐system Review Of Genotype–phenotype Correlationmentioning

confidence: 99%

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Genotype–phenotype correlates in Joubert syndrome: A review

Gana

Serpieri

Valente

2022

American J of Med Genetics Pt C

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Joubert syndrome (JS) is a genetically heterogeneous primary ciliopathy characterized by a pathognomonic cerebellar and brainstem malformation, the “molar tooth sign,” and variable organ involvement. Over 40 causative genes have been identified to date, explaining up to 94% of cases. To date, gene‐phenotype correlates have been delineated only for a handful of genes, directly translating into improved counseling and clinical care. For instance, JS individuals harboring pathogenic variants in TMEM67 have a significantly higher risk of liver fibrosis, while pathogenic variants in NPHP1, RPGRIP1L, and TMEM237 are frequently associated to JS with renal involvement, requiring a closer monitoring of liver parameters, or renal functioning. On the other hand, individuals with causal variants in the CEP290 or AHI1 need a closer surveillance for retinal dystrophy and, in case of CEP290, also for chronic kidney disease. These examples highlight how an accurate description of the range of clinical symptoms associated with defects in each causative gene, including the rare ones, would better address prognosis and help guiding a personalized management. This review proposes to address this issue by assessing the available literature, to confirm known, as well as to propose rare gene‐phenotype correlates in JS.

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Section: System‐by‐system Review Of Genotype–phenotype Correlationmentioning

confidence: 82%

Section: System‐by‐system Review Of Genotype–phenotype Correlationmentioning

confidence: 99%

Section: System‐by‐system Review Of Genotype–phenotype Correlationmentioning

confidence: 99%

Section: System‐by‐system Review Of Genotype–phenotype Correlationmentioning

confidence: 99%

See 2 more Smart Citations

Genotype–phenotype correlates in Joubert syndrome: A review

Gana

Serpieri

Valente

2022

American J of Med Genetics Pt C

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“…The OFD1 gene that may play a role in cortical and heart development (Zhang et al, 2020) is involved in JS. OFD1 mutations are inherited in an X-linked recessive fashion; males are affected, while female carriers are asymptomatic (Pezzella et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Case report and a brief review: Analysis and challenges of prenatal imaging phenotypes and genotypes in Joubert syndrome

Huang

Lu²,

Liu³

et al. 2022

Front. Genet.

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Prenatal imaging phenotypes and genotypes were analyzed in 13 cases prenatally diagnosed with Joubert syndrome (JS), all of which underwent magnetic resonance imaging (MRI), ultrasound, and genetic testing. Prenatal MRI diagnosed 10 cases as JS with a typical molar tooth sign (MTS), while prenatal ultrasound diagnosed or suspiciously diagnosed 11 cases as JS with typical or mild MTS in 10 cases. Mutations in JS-related genes and other prenatal JS imaging phenotypes were identified in 10 cases, including OFD1 in two cases [cerebellar vermis (CV) absence, posterior fossa dilation, ventriculomegaly, polydactyly, malformations of cortical development (MCD), and persistent left superior vena cava], TMEM67 in two cases (CV absence, polydactyly, hyperechoic kidneys or polycystic kidneys, posterior fossa dilation, and ventriculomegaly), CC2D2A in two cases (CV absence, polydactyly, MCD, agenesis of the corpus callosum, encephalocele and hydrocephalus, ventriculomegaly, and posterior fossa dilation), RPGRIP1L in one case (CV absence), TCTN3 in one case (CV absence, polydactyly, MCD, and posterior fossa dilation), CEP290 in one case (CV absence and polycystic kidney), and NPHP1 in one case (CV absence). The prenatal diagnosis of JS presents a number of challenges, including the variants of unknown significance, the lack of functional assessment in prenatal imaging, unclear phenotype–genotype relationships in prenatal evaluation, and the incorrect identification of the JS hallmark, the MTS, in prenatal imaging, especially on ultrasound. Although combined MRI, ultrasound, and exome sequencing could help improve the prenatal diagnosis of JS, there still exist significant challenges.

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OFD1: One gene, several disorders

Pezzella

Bove

Tammaro

et al. 2022

American J of Med Genetics Pt C

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The OFD1 protein is necessary for the formation of primary cilia and left–right asymmetry establishment but additional functions have also been ascribed to this multitask protein. When mutated, this protein results in a variety of phenotypes ranging from multiorgan involvement, such as OFD type I (OFDI) and Joubert syndromes (JBS10), and Primary ciliary dyskinesia (PCD), to the engagement of single tissues such as in the case of retinitis pigmentosa (RP23). The inheritance pattern of these condition differs from X‐linked dominant male‐lethal (OFDI) to X‐linked recessive (JBS10, PCD, and RP23). Distinctive biological peculiarities of the protein, which can contribute to explain the extreme clinical variability and the genetic mechanisms underlying the different disorders are discussed. The extensive spectrum of clinical manifestations observed in OFD1‐mutated patients represents a paradigmatic example of the complexity of genetic diseases. The elucidation of the mechanisms underlying this complexity will expand our comprehension of inherited disorders and will improve the clinical management of patients.

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A rare mutant of OFD1 gene responsible for Joubert syndrome with significant phenotype variation

Cited by 10 publications

References 17 publications

Genotype–phenotype correlates in Joubert syndrome: A review

Genotype–phenotype correlates in Joubert syndrome: A review

Case report and a brief review: Analysis and challenges of prenatal imaging phenotypes and genotypes in Joubert syndrome

OFD1: One gene, several disorders

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