Trio-Based Whole-Exome Sequencing Identifies a De novo EFNB1 Mutation as a Genetic Cause in Female Infant With Brain Anomaly and Developmental Delay

@article{Han2020TrioBasedWS,
  title={Trio-Based Whole-Exome Sequencing Identifies a De novo EFNB1 Mutation as a Genetic Cause in Female Infant With Brain Anomaly and Developmental Delay},
  author={Ji Yoon Han and Hyun Jeong Kim and Ja Hyun Jang and In Goo Lee and Joonhong Park},
  journal={Frontiers in Pediatrics},
  year={2020},
  volume={8}
}
Background: Craniofrontonasal syndrome is a rare, X-linked disorder in which heterozygous females ironically reported the majority of patients and is caused by in the EFNB1 gene located at chromosome Xq13.1. Unlike previous reports, we present a female infant with a de novo EFNB1 missense mutation that was demonstrated in clinical diagnosis as global developmental delay (GDD) and brain anomaly without frontonasal dysplasia or other malformation. Case Presentation: This study reports the genetic… 

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References

SHOWING 1-10 OF 32 REFERENCES

The origin of EFNB1 mutations in craniofrontonasal syndrome: frequent somatic mosaicism and explanation of the paucity of carrier males.

It is concluded that the major factor accounting for the relative scarcity of carrier males is the bias toward mutations in the paternal germline combined with reduced reproductive fitness in affected females.

Twenty‐six novel EFNB1 mutations in familial and sporadic craniofrontonasal syndrome (CFNS)

It is concluded that the major causes of familial as well as sporadic CFNS are loss of function mutations in the EFNB1 gene that comprise premature termination or abrogate receptor‐ligand interaction, oligomerization, and ephrin‐B1 reverse signaling.

Diagnostic value of exome and whole genome sequencing in craniosynostosis

Background Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ∼1 in 2250 births, either in isolation or as part of a syndrome. Mutations in at least 57 genes have been

Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes

A more severe outcome in mosaic is demonstrated than in constitutionally deficient males in an X-linked dominant disorder and provide further support for the cellular interference mechanism, normally related to X-inactivation in females.

A novel EFNB1 mutation (c.712delG) in a family with craniofrontonasal syndrome and diaphragmatic hernia

The occurrence of congenital diaphragmatic hernia, phenotypic differences between males and females, and utility of molecular testing in craniofrontonasal syndrome are demonstrated.

Craniofrontonasal syndrome in a male due to chromosomal mosaicism involving EFNB1: further insights into a genetic paradox

Evidence is provided that cellular interference contributes to the paradoxical inheritance pattern of CFNS andMosaicism for cell populations with different levels of EFNB1 expression can explain the severe phenotype of this patient.

Contiguous gene deletions involving EFNB1, OPHN1, PJA1 and EDA in patients with craniofrontonasal syndrome

Although it is too early to predict the future cognitive performance of the two infant patients with contiguous gene deletions of OPHN1–EFNB1–PJA1, mild learning disabilities have been recognized in the older, third patient.

A Novel Mutation in EFNB1, Probably with a Dominant Negative Effect, Underlying Craniofrontonasal Syndrome

A Thai woman with CFNS is reported, in whom a novel mutation was discovered: c.685_686insG, in exon 5 of EFNB1, which is the first insertion and the most 3′ point mutation inEFNB1 reported to date.

First Korean Patients with Craniofrontonasal Syndrome Confirmed by EFNB1 Analysis.

For the first time in Korea two girls with molecularly confirmed CFNS are reported, showing the typical craniofacial manifestations of CFNS, whereas the severity and the type of associated anomalies differed between them, suggesting phenotypic diversity for this disease.

Genetic Analysis of Syndromic and Nonsyndromic Patients With Craniosynostosis Identifies Novel Mutations in the TWIST1 and EFNB1 Genes

The contribution of molecular genetic analysis to the diagnosis of patients with syndromic craniosynostosis was useful because some were originally misdiagnosed, and thorough clinical evaluation can guide molecular testing and result in a correct diagnosis.