A novel intragenic deletion in OPHN1 in a Japanese patient with Dandy-Walker malformation

Iida, Aritoshi; Takeshita, Eri; Kosugi, Shunichi; Kamatani, Yoichiro; Momozawa, Yukihide; Kubo, Michiaki; Nakagawa, Eiji; Kurosawa, Kenji; Inoue, Ken; Goto, Yu Ichi

doi:10.1038/s41439-018-0032-8

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…To date, the mutations detected in the OPHN1 gene have been described in subjects with neurodevelopmental diseases such as ID, ataxia, epilepsy, seizure, and schizophrenia. [ 17 ]…”

Section: Discussionmentioning

confidence: 99%

Exon 21 deletion in the OPHN1 gene in a family with syndromic X-linked intellectual disability

Bogliș

Cosma²,

Tripon

et al. 2020

Medicine

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Introduction: The oligophrenin-1 ( OPHN1 ) gene, localized on the X chromosome, is a Rho-GTPase activating protein that is related to syndromic X-linked intellectual disability (XLID). XLID, characterized by brain anomalies, namely cerebellar hypoplasia, specific facial features, and intellectual disability, is produced by different mutations in the OPHN1 gene. Patient concerns: In this report, we present the clinical and molecular findings of a family affected by a mild XLID due to a deletion in the OPHN1 gene, exon 21, Xq12 region using Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The clinical features present in the family are a mild developmental delay, behavioral disturbances, facial dysmorphism, pes planus, nystagmus, strabismus, epilepsy, and occipital arachnoid cyst. Interventions: The MLPA analysis was performed for investigation of the copy number variations within the X chromosome for the family. Diagnosis and outcome: The MLPA analysis detected a deletion in the OPHN1 gene, exon 21 for the proband, and a heterozygous deletion for the probands mother. The deletion of the Xq12 region of maternal origin, including the exon 21 of the OPHN1 gene, confirmed for the probands nephew. Lessons: Our findings emphasize the utility of the MLPA analysis to identify deletions in the OPHN1 gene responsible for syndromic XLID. Therefore, we suggest that MLPA analysis should be performed as an alternative diagnostic test for all patients with a mild intellectual disability associated or not with behavioral disturbances, facial dysmorphism, and brain anomalies.

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“…To date, the mutations detected in the OPHN1 gene have been described in subjects with neurodevelopmental diseases such as ID, ataxia, epilepsy, seizure, and schizophrenia. [ 17 ]…”

Section: Discussionmentioning

confidence: 99%

Exon 21 deletion in the OPHN1 gene in a family with syndromic X-linked intellectual disability

Bogliș

Cosma²,

Tripon

et al. 2020

Medicine

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“…Additional features have been reported, including strabismus, epilepsy, behavioral disorders, and cerebellar dysplasia. Carrier females are usually unaffected, probably due to protective skewed inactivation of the X chromosome; nevertheless, some paucisymptomatic females have been reported (most with a random pattern of X inactivation), typically showing mild ID, minor cerebellar anomalies or strabismus (Bogliş et al, 2020; Des Portes et al, 2004; Iida et al, 2018; Moortgat et al, 2018; Schwartz et al, 2019; Zanni et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, it also includes an N‐terminal Bin/Amphiphysin/Rvs (BAR) domain followed by a Pleckstrin homology (PH) domain and a C‐terminal domain with three proline‐rich regions (amino acids 567/585, 629/639, and 735/748) containing multiple SH3 binding sites (Billuart et al, 1998; Fauchereau et al, 2003). The vast majority of identified mutations are loss of function, including large genomic deletions encompassing the whole gene, multi‐exonic deletions as well as nonsense, frameshift or canonical splice‐sites variants (Bogliş et al, 2020; Des Portes et al, 2004; Iida et al, 2018; Moortgat et al, 2018; Schwartz et al, 2019; Zanni et al, 2005). The critical RhoGAP domain is nearly invariably affected, likely resulting in constitutive activation of GTPase targets (Billuart et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Novel unconventional variants expand the allelic spectrum of OPHN1 gene

Nuovo

Branković

Caputi

et al. 2021

American J of Med Genetics Pt A

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Mutations in the OPHN1 gene cause a rare X‐linked recessive neurodevelopmental disorder characterized by intellectual disability, variably associated with cerebellar hypoplasia and distinctive facial appearance. In most of cases so far reported, the identified genomic variants involve the region encoding the central RhoGAP domain of the oligophrenin‐1 protein, and are predicted to result in a complete loss of function. By using a NGS‐based diagnostic approach, we identified three male and a female patients from two unrelated families carrying novel non‐disruptive OPHN1 variants (the in‐frame c.116_127 deletion and the missense c.2129C>T change, respectively), affecting either the BAR domain or the C‐terminus proline‐rich domain of the protein. Clinical and neuroimaging findings in the patients recapitulated the main features of OPHN1‐related syndrome, including developmental delay, intellectual disability, behavioral disorder, dysmorphic features, seizures, cerebellar hypoplasia, and ventriculomegaly. Yet, we observed a wide variability even among affected siblings, confirming the lack of clear genotype–phenotype correlation. Our results expand the allelic spectrum of OPHN1 and illustrate the challenges for clinical interpretation of non‐disruptive variants affecting X‐linked genes.

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A novel partial duplication in OPHN1, associated with vermis cerebellar hypoplasia, seizures and developmental delay

et al. 2022

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A novel intragenic deletion in OPHN1 in a Japanese patient with Dandy-Walker malformation

Cited by 4 publications

References 11 publications

Exon 21 deletion in the OPHN1 gene in a family with syndromic X-linked intellectual disability

Exon 21 deletion in the OPHN1 gene in a family with syndromic X-linked intellectual disability

Novel unconventional variants expand the allelic spectrum of OPHN1 gene

A novel partial duplication in OPHN1, associated with vermis cerebellar hypoplasia, seizures and developmental delay

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