Discordant organ laterality in monozygotic twins with primary ciliary dyskinesia

Noone, Peadar G.; Bali, Deeksha; Carson, Johnny L.; Sannuti, Aruna; Gipson, Clay L.; Ostrowski, Lawrence E.; Bromberg, Philip A.; Boucher, Richard C.; Knowles, Michael R.

doi:10.1002/(sici)1096-8628(19990115)82:2<155::aid-ajmg11>3.0.co;2-t

Cited by 67 publications

(44 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, other researchers have been unable to confirm discordant handedness in MZ twins [Derom et al, 1996]. This author knows of only one report in which MZ twins are discordant for visceral situs [Noone et al, 1999]. This occurred within the context of ciliary dyskinesia, in which absence of ciliary movement permits situs solitus and situs inversus in equal proportions.…”

Section: Other Examples Of Discordancementioning

confidence: 90%

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

Machin

2009

American J of Med Genetics Pt C

138

102

View full text Add to dashboard Cite

Monozygotic twins (MZ) are rarely absolutely “identical.” This review discusses the types of genetic/epigenetic and prenatal environmental post‐zygotic mechanisms that cause discordance within such twin pairs. Some of these mechanisms—ranging from heterokaryotypia to skewed X‐chromosome inactivation—may cause extreme discordance, but these extremes are merely the more emphatic examples of discordance that, to some degree, underlies the majority of MZ twin pairs. Because of the entrenched misconception that MZ twins are necessarily identical, many MZ twin pairs are mistakenly designated as dizygotic (DZ). Clinical benefits to accurate zygosity determination include correct solid organ transplantation matching, if one twin requires donation for a non‐genetically mediated disease; the opportunity of preventive management for disorders that do not manifest synchronously; and better counseling to parents regarding their individually unique, and often psychologically puzzling, twin offspring. In twin pairs with complex and confusing biological origins, more detailed zygosity testing may be required. For example, intermediate trigametic and tetragametic chimeric dizygotic twins are reviewed, some of whom are, nevertheless, monochorionic (MC). Because of inter‐fetal vascular anastomoses in MC twins, genetic results from blood samples may not accurately reflect discordance in solid organs. Previously, it was thought that MZ twinning was some sort of embryological fluke. However, familial monozygotic twinning is more common than suggested by the literature. Seven new families are presented in an accompanying paper. Despite the difficulties and dangers of twin pregnancy (especially so for MC twins), human twinning persists, and continues to both challenge and fascinate parents, clinicians and geneticists. © 2009 Wiley‐Liss, Inc.

show abstract

Section: Other Examples Of Discordancementioning

confidence: 90%

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

Machin

2009

American J of Med Genetics Pt C

138

102

View full text Add to dashboard Cite

show abstract

“…The absence of functional nodal cilia in this and other models has been associated with a randomization of left-right asymmetry. A randomization of left-right asymmetry is also a common feature of PCD with ϳ50% of patients demonstrating complete situs inversus (11,33). The recent results demonstrating the importance of nodal cilia in left-right determination provide a mechanism whereby a single mutation in an axonemal protein could cause situs inversus, infertility, and the chronic respiratory infections observed in PCD.…”

Section: Discussionmentioning

confidence: 99%

Identification of Dynein Heavy Chain 7 as an Inner Arm Component of Human Cilia That Is Synthesized but Not Assembled in a Case of Primary Ciliary Dyskinesia

Zhang

O’Neal

Randell

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Although the basic structure of the axoneme has been highly conserved throughout evolution, the varied functions of specialized axonemes require differences in structure and regulation. Cilia lining the respiratory tract propel mucus along airway surfaces, providing a critical function to the defense mechanisms of the pulmonary system, yet little is known of their molecular structure. We have identified and cloned a dynein heavy chain that is a component of the inner dynein arm. Bronchial epithelial cells were obtained from normal donors and from a patient with primary ciliary dyskinesia (PCD) whose cilia demonstrated an absence of inner dynein arms by electron microscopy. Cilia from normal and PCD cells were compared by gel electrophoresis, and mass spectrometry was used to identify DNAH7 as a protein absent in PCD cilia. The full-length DNAH7 cDNA was cloned and shares 68% similarity with an inner arm dynein heavy chain from Drosophila. DNAH7 was induced during ciliated cell differentiation, and immunohistochemistry demonstrated the presence of DNAH7 in normal cilia. In cilia from PCD cells, DNAH7 was undetectable, whereas intracellular DNAH7 was clearly present. These studies identify DNAH7 as an inner arm component of human cilia that is synthesized but not assembled in a case of PCD.The basic structure of the axoneme consisting of nine outer microtubule doublets surrounding a central pair (9 ϩ 2 arrangement) is one of the most highly conserved structures in all of cell biology (1, 2). The 9 ϩ 2 arrangement is found in many diverse organisms ranging from the flagella of Chlamydomonas and the gill cilia of freshwater mussels to the sperm flagella of sea urchins and respiratory tract cilia of humans. Despite the structural similarity, each of these axonemes is specialized for a particular function. Thus, the waveform of a sperm flagellum (3), which functions to propel the sperm forward, is very different from the coordinated beating of respiratory tract cilia, which function to transport mucus over airway surfaces (4). Moreover, the regulation of the activity of each specialized axoneme is also likely to be unique. For example, increases in Ca 2ϩ have been shown to stimulate ciliary beating of tracheal epithelial cells (5), whereas Paramecium cilia respond to increased Ca 2ϩ by reversing the direction of beating (6). These functional differences are a reflection of unique modifications of the structure and composition of each specialized axoneme. For example, Chlamydomonas flagella have three outer arm dynein heavy chains (DHCs) 1 (7), whereas outer arms from mammalian respiratory cilia have been reported to contain only two DHCs (8). Therefore, it is clear that although the basic structure and components of cilia and flagella are conserved, specialization of function has resulted in important variations of structure and regulation among the different motile axonemes.The Chlamydomonas flagellum represents the most thoroughly characterized axonemal structure. Through the use of readily obtained mutants and comp...

show abstract

“…Congenital disorders are labeled as PCDs. PCD is a phenotypically and genetically heterogeneous condition where polypeptide species within the axoneme of cilia, sperm flagella, ciliary membrane or matrix are defective (2,3) . Pathophysiologically, the underlying defect leads to accumulation of secretions and consequent recurrent sinusitis, bronchiectasis & infertility.…”

Section: Discussionmentioning

confidence: 99%

“…Patients usually present with chronic URTI and/or LRTI due to the ineffective mucociliary mechanism. Some male patients present later in life with sterility due to immotile spermatozoa while cases of semisterility in females have also been reported (2) . Occasionally, KS may be associated with the reversible airflow obstruction hence patient may present with respiratory distress (5) .…”

Section: Discussionmentioning

confidence: 99%

Kartagener’s Syndrome: Presenting in Fourth Decade

Sejwani¹,

Jha²,

Tamakuwala³

et al. 2017

IAM

View full text Add to dashboard Cite

Kartagener's Syndrome (KS) is a rare ciliopathic autosomal recessive genetic disorder characterized by a triad of situs inversus, bronchiectasis, and chronic sinusitis. Although Siewart first described this condition in 1904, it was Kartagener -a Swiss pediatrician, who recognized the etiological correlation between elements of the triad and reported four cases in 1933 1. It is a type of Primary Ciliary Dyskinesia (PCD). The frequency of KS is 1:32,000 to 1:50,000 live births. A 40-year-old male patient presented to the emergency department with complaints of fever, productive cough, dyspnea, and headache. He had a history or a recurrent cough for ten years with multiple hospitalizations. The patient had been married for 15 years and still had no offsprings for which he had been investigated previously which was suggestive of azoospermia. He was febrile with normal other vitals accept his respiratory rate which was 28 per minute with 88% saturation on room air. Apex beat could be localized on 5th ICS right side on mid clavicular line. On percussion heart, borders were confirmed on the right side with liver dullness on left side. On auscultation, S1S2 were heard on the right side with coarse, leathery crepitations on inspiration and rhonchi on expiration.On investigating further his ECG showed features of dextrocardia and chest roentgenography was suggestive of dextrocardia with aortic arch on right side of the trachea with gastro-hepatic transposition suggestive of situs inversus with bronchietatic changes. Further High resolution computed tomography was done to confirm those findings along with ultrasound of abdomen which showed liver in left upper quadrant and spleen in right upper quadrant. A skull roentgenogram was also done which was suggestive of sinusitis.The 'nasal saccharin transit time' test gave mucociliary clearance time of 60 minutes (Normal < 30 minutes). Thus patient was diagnosed with Kartagener's syndrome clinically and also on the basis of investigations. The patient was treated with oral steroids, bronchodilators, mucolytics, and antibiotics and over the course of 10 days patient gradually recovered and was discharged.

show abstract

Discordant organ laterality in monozygotic twins with primary ciliary dyskinesia

Cited by 67 publications

References 21 publications

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

Identification of Dynein Heavy Chain 7 as an Inner Arm Component of Human Cilia That Is Synthesized but Not Assembled in a Case of Primary Ciliary Dyskinesia

Kartagener’s Syndrome: Presenting in Fourth Decade

Contact Info

Product

Resources

About