An 8.4‐Mb 3q26.33‐3q28 microdeletion in a patient with blepharophimosis–intellectual disability syndrome and a review of the literature

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Key Clinical Message

3q26.33‐3q27.2 microdeletion can be classified as a clinical entity characterized by intrauterine growth retardation, feeding problems in infancy, short stature, intellectual disability, hypotonia, dysmorphic facial features (medially sparse eyebrows, narrow horizontal palpebral fissures, epicanthal folds, flat nasal bridge and tip, short philtrum, and downturned corners of mouth), and teeth and feet abnormalities.

Related collections

Most cited references 17

Record: found
Abstract: found
Article: not found

Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.

Jill Clayton-Smith, James O'Sullivan, Sarah Daly … (2011)

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS or Ohdo syndrome) is a multiple anomaly syndrome characterized by severe intellectual disability, blepharophimosis, and a mask-like facial appearance. A number of individuals with SBBYSS also have thyroid abnormalities and cleft palate. The condition usually occurs sporadically and is therefore presumed to be due in most cases to new dominant mutations. In individuals with SBBYSS, a whole-exome sequencing approach was used to demonstrate de novo protein-truncating mutations in the highly conserved histone acetyltransferase gene KAT6B (MYST4/MORF)) in three out of four individuals sequenced. Sanger sequencing was used to confirm truncating mutations of KAT6B, clustering in the final exon of the gene in all four individuals and in a further nine persons with typical SBBYSS. Where parental samples were available, the mutations were shown to have occurred de novo. During mammalian development KAT6B is upregulated specifically in the developing central nervous system, facial structures, and limb buds. The phenotypic features seen in the Qkf mouse, a hypomorphic Kat6b mutant, include small eyes, ventrally placed ears and long first digits that mirror the human phenotype. This is a further example of how perturbation of a protein involved in chromatin modification might give rise to a multisystem developmental disorder. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

0 comments Cited 45 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia.

Steven Skoda, A Wiestner, H de Waal … (1997)

Essential thrombocythaemia (ET) is a chronic myeloproliferative syndrome due to sustained proliferation of megakaryocytes, which results in elevated numbers of circulating platelets, thrombotic or haemorrhagic episodes and occasional leukaemic transformation. The cause of ET is unknown. Hereditary thrombocythaemia (HT) with autosomal-dominant transmission has been described with manifestations similar to those of sporadic ET. As the thrombopoietin gene (THPO) encodes a lineage-restricted growth factor with profound stimulatory effects on megakaryopoiesis and platelet production, we tested the hypothesis that HT results from a mutation in the human THPO gene. In a Dutch family with eleven affected individuals, the thrombopoietin protein (TPO) concentrations in serum were consistently elevated in individuals with HT. We derived an intragenic CA marker for the human THPO gene and performed linkage analysis in fourteen informative meioses in this family. This resulted in a lod score of 3.5 at theta=0. A G-->C transversion was found in the splice donor site of intron 3 of the THPO gene in all affected family members. This mutation leads to THPO mRNAs with shortened 5'-untranslated regions (UTR) that are more efficiently translated than the normal THPO transcripts. We conclude that a splice donor mutation in THPO leads to systemic overproduction of TPO and causes thrombocythaemia.

0 comments Cited 41 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis.

Ian C Scott, Ira L Blitz, William N. Pappano … (1999)

Vertebrate bone morphogenetic protein 1 (BMP-1) and Drosophila Tolloid (TLD) are prototypes of a family of metalloproteases with important roles in various developmental events. BMP-1 affects morphogenesis, at least partly, via biosynthetic processing of fibrillar collagens, while TLD affects dorsal-ventral patterning by releasing TGFbeta-like ligands from latent complexes with the secreted protein Short Gastrulation (SOG). Here, in a screen for additional mammalian members of this family of developmental proteases, we identify novel family member mammalian Tolloid-like 2 (mTLL-2) and compare enzymatic activities and expression domains of all four known mammalian BMP-1/TLD-like proteases [BMP-1, mammalian Tolloid (mTLD), mammalian Tolloid-like 1 (mTLL-1), and mTLL-2]. Despite high sequence similarities, distinct differences are shown in ability to process fibrillar collagen precursors and to cleave Chordin, the vertebrate orthologue of SOG. As previously demonstrated for BMP-1 and mTLD, mTLL-1 is shown to specifically process procollagen C-propeptides at the physiologically relevant site, while mTLL-2 is shown to lack this activity. BMP-1 and mTLL-1 are shown to cleave Chordin, at sites similar to procollagen C-propeptide cleavage sites, and to counteract dorsalizing effects of Chordin upon overexpression in Xenopus embryos. Proteases mTLD and mTLL-2 do not cleave Chordin. Differences in enzymatic activities and expression domains of the four proteases suggest BMP-1 as the major Chordin antagonist in early mammalian embryogenesis and in pre- and postnatal skeletogenesis. Copyright 1999 Academic Press.

0 comments Cited 38 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Clin Case Rep

Journal ID (iso-abbrev): Clin Case Rep

Journal ID (doi): 10.1002/(ISSN)2050-0904

Journal ID (publisher-id): CCR3

Title: Clinical Case Reports

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2050-0904

Publication date (Electronic): 22 July 2016

Publication date Collection: August 2016

Volume: 4

Issue: 8 ( doiID: 10.1111/ccr3.2016.4.issue-8 )

Pages: 824-830

Affiliations

[ ¹ ] Department of Genetics United LaboratoriesTartu University Hospital TartuEstonia

[ ² ] Department of PediatricsInstitute of Clinical Medicine University of Tartu TartuEstonia

[ ³ ] Institute of Biomedicine and Translational Medicine Department of BiomedicineUniversity of Tartu TartuEstonia

[ ⁴ ] Institute of Molecular and Cell BiologyUniversity of Tartu TartuEstonia

Author notes

[*] [* ] Correspondence

Katrin Õunap, Department of Genetics, United Laboratories, Tartu University Hospital, 2 L. Puusepa Street, Tartu 51014, Estonia. Tel: + (372) 7 319 491; Fax: + (372) 7 319 484; E‐mail: katrin.ounap@ 123456kliinikum.ee

Article

Publisher ID: CCR3632

DOI: 10.1002/ccr3.632

PMC ID: 4974439

PubMed ID: 27525095

SO-VID: 8a14615f-9040-486f-adbf-5e595cacba3c

License:

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

History

Date received : 03 May 2015

Date revision received : 19 February 2016

Date accepted : 16 June 2016

Page count

Pages: 7

Funding

Funded by: Estonian Science Foundation

Award ID: PUT355

Custom metadata

source-schema-version-number 2.0

component-id ccr3632

cover-date August 2016

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.4 mode:remove_FC converted:05.08.2016

Keywords: 3q26.33‐3q27.2 microdeletion,3q27.3 microdeletion,blepharophimosis,intellectual disability,ohdo syndrome

Data availability:

Keywords: 3q26.33‐3q27.2 microdeletion, 3q27.3 microdeletion, blepharophimosis, intellectual disability, ohdo syndrome

An 8.4‐Mb 3q26.33‐3q28 microdeletion in a patient with blepharophimosis–intellectual disability syndrome and a review of the literature

Read this article at

Key Clinical Message

Related collections

ScienceOpen Clinical Case Reports Collection

Most cited references 17

Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.

An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia.

Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis.

Author and article information

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 433

Cited by 2

Most referenced authors 317