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

  title={Contiguous gene deletions involving EFNB1, OPHN1, PJA1 and EDA in patients with craniofrontonasal syndrome},
  author={Ilse Wieland and Christine Weidner and Roberto Ciccone and Elisabetta Lapi and Donna M. McDonald-McGinn and Wolfram Kress and Sibylle Jakubiczka and Hartmut Collmann and Orsetta Zuffardi and Elaine Zackai and Peter F Wieacker},
  journal={Clinical Genetics},
Craniofrontonasal syndrome (CFNS [MIM 304110]) is an X‐linked malformation syndrome characterized by craniofrontonasal dysplasia and extracranial manifestations in heterozygous females. In the majority of patients CFNS is caused by mutations in the EFNB1 gene (MIM 300035). We identified three girls with classical CFNS and mild developmental delay harboring de novo deletions of the EFNB1 gene. Applying haplotype analysis, Southern blot hybridization and array‐comparative genomic hybridization… 

A Novel de Novo Mutation Within EFNB1 Gene in a Young Girl with Craniofrontonasal Syndrome

A novel de novo missense mutation 373G>A was identified within the EFNB1 gene, leading to the replacement of glutamic acid at amino acid position 125 with lysine, which is expected to disrupt the interaction between the Eph receptor and ephrin B1 ligand, thus leading to craniofrontonasal syndrome.

Potocki–shaffer deletion encompassing ALX4 in a patient with frontonasal dysplasia phenotype

A female patient presenting with severe FND features along with partial alopecia, hypogonadism and intellectual disability is reported on, and comparative genomic hybridization techniques showed a large heterozygous de novo deletion at 11p11.12p12, encompassing the ALX4 gene.

Craniofrontonasal Syndrome Caused by Introduction of a Novel uATG in the 5′UTR of EFNB1

This study demonstrates, for the first time, the regulatory impact of uATG formation onEFNB1 levels and suggests that this should be the target region in molecular diagnosis of CFNS cases without pathogenic variants in the coding and splice sites regions of EFNB1.

Dissecting the molecular mechanisms in craniofrontonasal syndrome: differential mRNA expression of mutant EFNB1 and the cellular mosaic

Expression of EFNB1 mRNA was studied by RT-PCR in fibroblast cultures established from CFNS female patients to suggest differential degradation of mutant EF NB1 transcripts by the nonsense-mediated mRNA decay pathway, further supporting the concept of cellular interference in CFNS.

The impact of CFNS-causing EFNB1 mutations on ephrin-B1 function

Pathogenic mechanisms in CFNS manifestation include impaired ephrin-B1 signalling combined with cellular interference, and missense mutations located in the extracellular ephrine domain involved in Eph-ephrin-B 1 recognition and higher order complex formation are studied.

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

EFNB1 mutation is considered for a child with schizencephaly, and further study focusing on phenotyping is required to understand the possible contribution of environmental impact and genetic modifier in the expression of EFNB1.



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.

Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome.

It is concluded that mutations in EFNB1 cause CFNS, a X-linked craniofacial disorder with an unusual manifestation pattern, in which affected females show multiple skeletal malformations whereas the genetic defect causes no or only mild abnormalities in male carriers.

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.

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.

Mutational spectrum of the ED1 gene in X-linked hypohidrotic ectodermal dysplasia

This study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ED1 gene, as 56 different mutations reported in 85 independent patients are tabulated.

Expanding the phenotype of craniofrontonasal syndrome: two unrelated boys with EFNB1 mutations and congenital diaphragmatic hernia

Two unrelated families are described, in both of which a mother and her son have proven mutations in EFNB1, highlighting an important role for signalling by ephrin-B1 in the development of the diaphragm.

Clinical and genetic aspects of craniofrontonasal syndrome: towards resolving a genetic paradox.

Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome.

  • S. TwiggR. Kan A. Wilkie
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2004
It is proposed that in heterozygous females, patchwork loss of ephrin-B1 disturbs tissue boundary formation at the developing coronal suture, whereas in males deficient in ephin-B 1, an alternative mechanism maintains the normal boundary.

Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia

The findings give further support for the involvement of the oligophrenin-1 gene in specific morphological abnormalities of the brain which is of importance in the investigation of male patients presenting with mental retardation.

Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia.

Findings indicate that OPHN1 mutations result in a recognizable syndrome, and identification of O PHN1 as a further gene associated with epileptic seizures will help to unravel aetiologic factors of epilepsy.