Webbed toes and autism free#

Over time, the phenotype broadened to include varying degrees of developmental and motoric delay, microcephaly, and a variety of minor anomalies. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.Дubowitz syndrome was originally described in 1965 in a girl with intrauterine growth retardation (IUGR), eczema, short stature, failure to thrive, a high-pitched cry, presumed autosomal recessive inheritance and a distinctive facies (large, low set ears, retrognathia, ptosis, prominent nasal bridge), akin to Bloom and Seckel syndromes.

There are no patents, products in development or marketed products to declare. Leslie Biesecker receives royalties from Genentech Corporation and is an uncompensated consultant to the Illumina Corporation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Д¬ompeting interests: Lisa Leathwood and Maureen Risch both of Westat, Inc (supported by NCI contract number HHSN261201100018C) were involved in data collection, specifically, recruitment of patients 1 and 2. The work is made available under the Creative Commons CC0 public domain dedication.ДЇunding: This work was supported by the Division of Intramural Research of the National Human Genome Research Institute (NHGRI) and the Division of Cancer Epidemiology and Genetics (DCEG) of the National Cancer Institute's Intramural Research Program.

Webbed toes and autism free#

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Received: SeptemAccepted: Published: June 3, 2014 PLoS ONE 9(6):Д®ditor: Ralf Krahe, University of Texas MD Anderson Cancer Center, United States of America (2014) Dubowitz Syndrome Is a Complex Comprised of Multiple, Genetically Distinct and Phenotypically Overlapping Disorders. As a clinical entity, Dubowitz syndrome will need continual re-evaluation and re-definition as its constituent phenotypes are determined.Д¬itation: Stewart DR, Pemov A, Johnston JJ, Sapp JC, Yeager M, He J, et al. Taken together, our work and other reports on Dubowitz syndrome, as currently recognized, suggest that it is not a unitary entity but instead a collection of phenotypically similar disorders. Our work suggests that, in addition to dyskeratosis congenita, LIG4 and 17q24.2 syndromes also feature shortened telomeres to confirm this, telomere length testing should be considered in both disorders. In all three patients, a median lymphocyte telomere length of в‰¤1 st centile was observed and radiosensitivity assays showed increased sensitivity to ionizing radiation. In the third patient, array SNP genotyping revealed a de novo в€ј3.89 Mb interstitial deletion at chromosome 17q24.2 (chr 17:62,068,463вЂ“65,963,102, hg18), which spanned the known Carney complex gene PRKAR1A. Western blotting showed an absence of a ligase IV band in both siblings. These LIG4 mutations were previously reported in the sibling sister her brother had not been previously tested. The frameshift mutation has not been reported in 1000 Genomes, ESP, or ClinSeq. In the siblings, exome sequencing identified compound heterozygosity for a known rare nonsense substitution in the nuclear ligase gene LIG4 (rs104894419, NM_002312.3:c.2440C>T) that predicts p.Arg814X (MAF:0.0002) and an NM_002312.3:c.613delT variant that predicts a p.Ser205Leufs*29 frameshift. Given the siblings' history of bone marrow abnormalities, we also evaluated telomere length and performed radiosensitivity assays.

We clinically characterized and performed exome sequencing and high-density array SNP genotyping on three individuals with Dubowitz syndrome, including a pair of previously-described siblings (Patients 1 and 2, brother and sister) and an unpublished patient (Patient 3). There is considerable phenotypic variability, suggesting genetic heterogeneity. Dubowitz syndrome is a rare disorder characterized by multiple congenital anomalies, cognitive delay, growth failure, an immune defect, and an increased risk of blood dyscrasia and malignancy.