-
Genetics and Molecular Research : GMR Jun 2016Short rib-polydactyly syndrome type III (SRPS3) is a perinatal lethal skeletal disorder with polydactyly and multisystem organ abnormalities. While ultrasound of the...
Short rib-polydactyly syndrome type III (SRPS3) is a perinatal lethal skeletal disorder with polydactyly and multisystem organ abnormalities. While ultrasound of the fetus can detect skeletal abnormalities characteristic of SRPS3, the syndrome is often difficult to diagnose before birth. As SRPS3 is an autosomal recessive disorder, identification of the gene mutations involved could lead to the development of prenatal genetic testing as an accurate method of diagnosis. In this study, we describe genetic screening approaches to identify potential abnormalities associated with SRPS3. Karyotype analysis, array comparative genomic hybridization (aCGH), and next-generation panel sequencing were each performed on a fetus showing signs of the disorder, as well as on the mother and father. Karyotype and aCGH results revealed no abnormalities. However, next-generation panel sequencing identified novel mutations in the DYNC2H1 gene. The fetus was compound heterozygous for both a missense mutation c.8313A > T and a frameshift mutation c.10711_10714delTTTA in the DYNC2H1 gene, which were inherited from the mother and father, respectively. These variants were further confirmed using Sanger sequencing and have not been previously reported. Our study indicates the utility of using next-generation panel sequencing in screening for novel disease-associated mutations.
Topics: Adult; Comparative Genomic Hybridization; Cytoplasmic Dyneins; Female; Fetus; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Karyotype; Mutation; Pedigree; Short Rib-Polydactyly Syndrome
PubMed: 27323140
DOI: 10.4238/gmr.15028134 -
The Journal of Maternal-fetal &... Dec 2023Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM # 613091) represents a clinical spectrum encompassing a heterogeneous group of skeletal dysplasias...
Early prenatal diagnosis of a recurrent case of short-rib thoracic dysplasia 3 due to compound heterozygosity for variations in the DYNC2H1 gene: an "ultrasound first" approach.
Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM # 613091) represents a clinical spectrum encompassing a heterogeneous group of skeletal dysplasias associated with homozygous or compound heterozygous mutations of DYNC2H1. We describe the case of a couple with two consecutive therapeutic abortions due to a diagnosis of short-rib thoracic dysplasia mutations. In the first pregnancy, the diagnosis has been made at 21 weeks. In the second one, an accurate and early ultrasound examination allowed a diagnosis at 12 weeks. DYNC2H1 mutations were confirmed in both cases. In this report, we underline the importance of an ultrasound evaluation at the end of the first trimester of pregnancy in the detection of early signs of skeletal dysplasias. An early prenatal diagnosis of a short-rib skeletal dysplasia, such as for other severe skeletal dysplasias, is critical to offer a couple the chance of a weighted, informed, and less traumatic decision about the continuation of the pregnancy.
Topics: Pregnancy; Female; Humans; Short Rib-Polydactyly Syndrome; Prenatal Diagnosis; Ultrasonography; Osteochondrodysplasias; Ribs; Ultrasonography, Prenatal; Cytoplasmic Dyneins
PubMed: 37100787
DOI: 10.1080/14767058.2023.2205985 -
Journal of Postgraduate Medicine 2020
Topics: Adaptor Proteins, Signal Transducing; Cytoskeletal Proteins; Dyspnea; Fever; Growth Plate; Humans; Infant; Male; Radiography; Ribs; Short Rib-Polydactyly Syndrome; Sweating
PubMed: 33037165
DOI: 10.4103/jpgm.JPGM_4_20 -
Genetics in Medicine : Official Journal... Jan 2021
PubMed: 33169000
DOI: 10.1038/s41436-020-01033-5 -
American Journal of Human Genetics Aug 2015KIAA0586, the human ortholog of chicken TALPID3, is a centrosomal protein that is essential for primary ciliogenesis. Its disruption in animal models causes defects...
KIAA0586, the human ortholog of chicken TALPID3, is a centrosomal protein that is essential for primary ciliogenesis. Its disruption in animal models causes defects attributed to abnormal hedgehog signaling; these defects include polydactyly and abnormal dorsoventral patterning of the neural tube. Here, we report homozygous mutations of KIAA0586 in four families affected by lethal ciliopathies ranging from a hydrolethalus phenotype to short-rib polydactyly. We show defective ciliogenesis, as well as abnormal response to SHH-signaling activation in cells derived from affected individuals, consistent with a role of KIAA0586 in primary cilia biogenesis. Whereas centriolar maturation seemed unaffected in mutant cells, we observed an abnormal extended pattern of CEP290, a centriolar satellite protein previously associated with ciliopathies. Our data show the crucial role of KIAA0586 in human primary ciliogenesis and subsequent abnormal hedgehog signaling through abnormal GLI3 processing. Our results thus establish that KIAA0586 mutations cause lethal ciliopathies.
Topics: Base Sequence; Cell Cycle Proteins; Ciliary Motility Disorders; Codon, Nonsense; Europe, Eastern; Fatal Outcome; Founder Effect; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; Hydrocephalus; Likelihood Functions; Molecular Sequence Data; Pedigree; Phenotype; Sequence Analysis, DNA; Short Rib-Polydactyly Syndrome
PubMed: 26166481
DOI: 10.1016/j.ajhg.2015.06.003 -
Cureus Sep 2020Microcephalic osteodysplastic primordial dwarfism type 2 (MOPD2) is a rare autosomal recessive disorder that presents as a myriad of skeletal abnormalities collectively...
Microcephalic osteodysplastic primordial dwarfism type 2 (MOPD2) is a rare autosomal recessive disorder that presents as a myriad of skeletal abnormalities collectively termed as osteodysplasia, which have their onset during intrauterine life with the fetus exhibiting intrauterine growth restriction. Affected individuals also tend to have a very small head size that is more than three standard deviations (SD) below the mean for a population termed microcephalic. The growth problems progress postnatally, causing stunted growth or short stature. In this report, we present the case of two siblings: a 15-year-old unvaccinated female weighing 8 kg (case one), and a seven-year-old unvaccinated female weighing 6 kg (case two), who presented to the Department of Pediatrics, Unit 2 at the Civil Hospital in Karachi, Pakistan, complaining of short stature since birth.
PubMed: 33042696
DOI: 10.7759/cureus.10258 -
Taiwanese Journal of Obstetrics &... Aug 2018
Corrigendum to "Identification of a c.544C>T mutation in WDR34 as a deleterious recessive allele of short rib-polydactyly syndrome" [Taiwanese Journal of Obstetrics & Gynecology 56 (2017) 857-862].
PubMed: 30122595
DOI: 10.1016/j.tjog.2018.06.031 -
Kardiologia Polska Sep 2019
Anomalous origin of the right coronary artery from the left Valsalva sinus in a patient presenting with syncope, ventricular tachycardia, and electrocardiographic early repolarization pattern.
Topics: Coronary Angiography; Coronary Vessel Anomalies; Electrocardiography; Humans; Middle Aged; Sinus of Valsalva; Syncope; Syndrome; Tachycardia, Ventricular
PubMed: 31354160
DOI: 10.33963/KP.14909