We have located links that may give you full text access.
DISP1 deficiency: monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations.
PURPOSE: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog (SHH), a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with DISP1 variants.
METHODS: This study was based on the identification of at least one pathogenic variant of the DISP1 gene in individuals for whom detailed clinical data were available.
RESULTS: A total of 23 DISP1 variants were identified in heterozygous, compound heterozygous or homozygous states in 25 individuals with midline craniofacial defects. Most cases were minor forms of HPE, with craniofacial features such as orofacial cleft, solitary median maxillary central incisor (SMMCI), and congenital nasal pyriform aperture stenosis (CNPAS). These individuals had either monoallelic loss-of-function variants or biallelic missense variants in DISP1. In individuals with severe HPE, the DISP1 variants were commonly found associated with a variant in another HPE-linked gene (i.e. oligogenic inheritance).
CONCLUSION: The genetic findings we have acquired demonstrate a significant involvement of DISP1 variants in the phenotypic spectrum of midline defects. This underlines its importance as a crucial element in the efficient secretion of SHH. We also demonstrated that the very rare SMMCI-CNPAS combination is part of the DISP1-related phenotype. The present study highlights the clinical risks to be flagged up during genetic counseling after the discovery of a pathogenic DISP1 variant.
METHODS: This study was based on the identification of at least one pathogenic variant of the DISP1 gene in individuals for whom detailed clinical data were available.
RESULTS: A total of 23 DISP1 variants were identified in heterozygous, compound heterozygous or homozygous states in 25 individuals with midline craniofacial defects. Most cases were minor forms of HPE, with craniofacial features such as orofacial cleft, solitary median maxillary central incisor (SMMCI), and congenital nasal pyriform aperture stenosis (CNPAS). These individuals had either monoallelic loss-of-function variants or biallelic missense variants in DISP1. In individuals with severe HPE, the DISP1 variants were commonly found associated with a variant in another HPE-linked gene (i.e. oligogenic inheritance).
CONCLUSION: The genetic findings we have acquired demonstrate a significant involvement of DISP1 variants in the phenotypic spectrum of midline defects. This underlines its importance as a crucial element in the efficient secretion of SHH. We also demonstrated that the very rare SMMCI-CNPAS combination is part of the DISP1-related phenotype. The present study highlights the clinical risks to be flagged up during genetic counseling after the discovery of a pathogenic DISP1 variant.
Full text links
Related Resources
Trending Papers
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Prevention and treatment of ischaemic and haemorrhagic stroke in people with diabetes mellitus: a focus on glucose control and comorbidities.Diabetologia 2024 April 17
British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease.Rheumatology 2024 April 17
Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.Circulation 2024 April 19
Albumin: a comprehensive review and practical guideline for clinical use.European Journal of Clinical Pharmacology 2024 April 13
Eosinophilic Esophagitis: Clinical Pearls for Primary Care Providers and Gastroenterologists.Mayo Clinic Proceedings 2024 April
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app