Maternal Mosaicism

Leave a comment

Inheritance mosaicism2

This new article by Emma Bedoukian and collegues present the first report of germline inheritance of Bohring-Opitz Syndrome.
“[…] Most patients [affected with Bohring-Opitz Syndrome (BOS)] […] have a de novo nonsense or frameshift variant in ASXL1. We report a case of BOS caused by a pathogenic ASXL1 variant inherited from a germline mosaic mother. The ASXL1 mutation was detected via trio exome sequencing. The sequencing data demonstrated that the variant was inherited maternally but that the maternal variant was underrepresented in comparison to the normal allele. These results suggested maternal mosaicism for the variant. Additional testing on the mother was performed on buccal cell DNA, which was also consistent with mosaicism. The mother had been reported to be healthy and the family history is unremarkable. This is the first report of BOS caused by a mutation inherited from an unaffected, presumed germline mosaic parent. This phenomenon has been reported for other traditionally de novo dominant disorders like CHARGE syndrome and Cornelia de Lange syndrome. This case emphasizes the need for accurate low but non‐negative recurrence risk counseling for families with children with BOS and it impacts exome interpretation strategy.”

» Bedoukian E, Copenheaver D, Bale S, Deardorff M. Bohring‐Opitz syndrome caused by an ASXL1 mutation inherited from a germline mosaic mother. Am J Med Genet Part A. 2018;176A:1249–1252. https://doi.org/10.1002/ajmg.a.38686

Inheritance mosaicism1

In most of the cases Bohring-Opitz syndrome (BOS) is the result of a novo mutation in the  ASXL1 gene. The risk of having another child with Bohring-Opitz Syndrome is low. (Russell, B. et al. 2018)

Inheritance de novo

»Read also our blog post https://bohring-opitz.org/2017/10/30/bos-inherited-by-germline-mosaicism/

Research for ASXL Syndromes

Leave a comment

fall back imageWe are thrilled to announce the launch of the ASXL Rare Research Endowment (AЯRE) Foundation (www.arrefoundation.org)! AЯRE will provide sustainable support for evidence-based research that will increase our understanding of the ASXL genes and improve the treatment of individuals with congenital ASXL mutations.

Our ASXL families — who have Bohring-Opitz Syndrome (ASXL1), Bainbridge-Ropers Syndrome (ASXL3), and Shashi-Pena Syndrome (ASXL2) – face extraordinary challenges and uncertainty. AЯRE will bring together the medical and scientific leaders to study ASXL genes and clinical challenges so that we can improve care management strategies, assist with patient advocacy, and ultimately introduce potential treatments/cure.

I would like to thank our incredible team of officers & board volunteers for all their efforts to make this possible! We are on this journey together and need your help to realize this vision. Please consider to rally family & friends to support this important cause through volunteer efforts and donations.

VOLUNTEER

DONATE

AЯRE has more exciting news and actionable information ahead. Check out our website (www.arrefoundation.org) to learn more about our plans, join us on Facebook, and sign up for our newsletters.

NEWSLETTER

Our ASXL children are an incredible inspiration and have changed our perspective on life. Let’s join together so that we can become stronger advocates and provide our children with the best lives possible.

I am excited about our road ahead and look forward to hearing from you!

Best,
Laura Badmaev
Chair, AЯRE Foundation
laura@arrefoundation.org

 

 

Bohring-Opitz Syndrome

Leave a comment

genereview

Bianca Russell, Wen-Hann Tan and John M Graham have published a new comprehensive overview about Bohring-Opitz Syndrome (BOS) in GeneReviews.

After the publication of the Unique leaflet by Joanna Kennedy (2017), the “Clinical management of patients with ASXL1 mutation and Bohring-Opitz Syndrome […]” by Bianca Russell and colleagues (2015) and previously published article about BOS (Magini, P. et al. 2012, Hoischen, A. et al. 2011 and Hasting,R. et al. 2011) this review is an excellent resource to understand and learn about Bohring-Opitz Syndrome. Part of the publication are summary, diagnosis, clinical characteristics, genetically related disorders and management of Bohring-Opitz Syndrome as well as genetic counselling and because it is written in understandable language it is an exceptional reference work not only for experts but for parents also!

Please read the full text of “Bohring-Opitz Syndrome” here: https://www.ncbi.nlm.nih.gov/books/NBK481833/

Germline mutation but no BOS

Leave a comment

We have learned that  germline mutations of human ASXL1 is the cause of Bohring-Opitz  syndrome (BOS). Germline means its a novo ASXL1 mutation, the gene mutates at conception, creating a developmental disorder that leads to BOS. Patients with somatic ASXL1 mutation (the mutation formed during later life) have an increased risk of myelodysplasia (MDS), myeloproliferative neoplasms (MPN), and acute myeloid leukemia (AML) acute myeloid leukemia (AML), forms of blood cancer.

Karen Seiter and colleges present a father and son who have a identical mutation of ASXL1 with the inference that these cases support the diagnosis of a germline mutation of ASXL1. Interestingly this specific mutation has been reported in one case of Bohring-Opitz syndrome. Both, father and son have developed myelodysplasia to myeloid leukemia but have no Bohring-Opitz Syndrome.

» Read here the article of Karen Seiter and colleges: “Acute myeloid leukemia in a father and son with a germline mutation of ASXL1″ (Biomarker Research 20186:7, https://doi.org/10.1186/s40364-018-0121-3)

News from the ASXL Registry

Leave a comment

Exciting news from the ASXL Registry! Out of 33 families who have completed the  enrolment, 15 surveys are completed! To obtain accurate knowledge about causes, symptoms, quality of life and treatments for Bohring-Opitz Syndrome, it is important that more families enrol the ASXL Registry and we need your support. A well run registry helps produce scientific literature and leads to research findings which is crucial to help our children live a better life.

Do you want to be part of the ASXL Registry? Please follow these steps:

  • Step 1: Email ASXLRegistry@cchmc.org
  • Step 2: 15-30 minute phone call to review the consent form and answer questions
  • Step 3: Sign consent form and send it back.

More information you can find in the first newsletter of the ASXL Registry!

Thank you!

Documentary worldwide

Leave a comment

KULUUT, the documentary about Coen and his family finding happiness despite of living with a syndrome, can now be seen worldwide. Until now it was broadcasted just for the Dutch public, but now we all can enjoy this beautiful and eagerly awaited documentary worldwide! Coen has the rare Bohring-Opitz Syndrome and we, the BOS Family are extremely grateful that Charlotte Driessen made this film possible. Kuluut has won international attention and received several film awards. The documentary won a Hollywood International Independent Documentary Awards Award in the category of First Time Filmmaker, after that it won a Kudos Endeavor Award in the Docs Without Borders Film Festival competition and was also an official selection as a semi finalist in the Atlanta DocuFest.

Our thanks go out to the makers of KULUT and the wonderful family of Coen!

Merry Christmas!

Kuluut – English subtitles from Charlotte Driessen on Vimeo.

 

New cause for BOS?

Leave a comment

Researchers have expanded the clinical spectrum of KLHL7 […] by describing a syndrome with features overlapping CS/CISS1 (Crisponi syndrome/cold-induced sweating syndrome type 1) and Bohring-Opitz Syndrome (BOS). At six patients with microcephaly, facial dysmorphism, including exophthalmos, nevus flammeus of the glabella and joint contractures with a suspected BOS posture in five out of six patients they found with whole-exome sequencing (WES) mutations in the KLHL7 gene.

Prior to 2011, geneticists relied on making a clinical diagnosis by recognizing the distinguishable physical characteristics in the appearance of their patients. In 2011, researchers at the Radboud University Nijmegen medical centre discovered one genetic cause of Bohring-Opitz Syndrome. They found that seven of 13 examined patients with the BOS phenotype had the novo mutation in the ASXL1 gene. However another six children with clinical diagnosis of BOS didn’t have this mutation, this indicates that other genes may be involved in this syndrome suggesting clinical and genetic heterogeneity, meaning there must be at least one other cause of BOS.

»Bruel A, Bigoni S, Kennedy J, et al: Expanding the clinical spectrum of recessive truncating mutations of KLHL7 to a Bohring-Opitz-like phenotype. Journal of Medical Genetics Published Online First: 26 October 2017. doi: 10.1136/jmedgenet-2017-104748

 

BOS inherited by germline mosaicism

1 Comment

“This is the first report of Bohring-Opitz syndrome caused by a mutation inherited from an unaffected, somatic mosaic parent with presumed germline mosaicism. This phenomenon has been reported for other traditionally de novo dominant disorders like CHARGE syndrome and Cornelia de Lange syndrome (2)(3). This case demonstrates that haploinsufficiency of ASXL1 is not lethal in the germline, and emphasizes the need for accurate low but non-negative recurrence risk counseling for families with children with Bohring-Opitz syndrome.” – Deborah Copenheaver et.al.

The BOS Registry

4 Comments

BOS registry 10

Our best chance to help individuals who are affected by Bohring-Opitz Syndrome (BOS) is a registry that will collect important information about raising a child with BOS and their medical history and build a resource for a better understanding of this rare disease for patients, caregivers as well for medical professionals.

The amount knowledge started small, with just four patients presented by Axel Bohring in 1999. Over the years, more and more cases were presented and our BOS Family is still growing.

The BOS & ASXL REGISTRY is here! We need your help in building such a resource and encourage you to become part of the “Bohring-Opitz Syndrome (BOS) & ASXL related Registry”. This registry, created by Dr. Bianca Russell and Dr. Wen-Hann Tan, is a milestone in the history of Bohring-Opitz Syndrome and the more people registered, the more valid and valuable the information becomes, which will result in a significant step in improving the lives of people affected with Bohring-Opitz Syndrome.

»Learn more about the registry!

Thank you for considering having your child or BOS-Angel join the registry. Your participation makes the difference!