Primary ciliary dyskinesia: Kartagener syndrome in a family with a novel DNAH5 gene mutation and variable phenotypes

Abstract

Background: Primary ciliary dyskinesia is a genetically heterogeneous autosomal recessive disorder with variable clinical manifestations, including chronic rhinosinusitis, otitis media, bronchitis, pneumonia, bronchiectasis, situs inversus totalis, reduced fertility in female patients and male infertility. The condition occurs as a result of abnormal ciliary structure and function. It is presented in early life with an estimated incidence of approximately 1/16,000-20,000. About 50% of the affected patients have situs inversus totalis leading to Kartagener syndrome (MIM: 244400). So far more than 19 causative genes have been associated with primary ciliary dyskinesia.Case report: Here we are presenting Kartagener syndrome in a consanguineous Kuwaiti family with a novel pathogenic DNAH5 gene mutation; namely c.9864dupA; [p.Pro3289ThrfsStop52], which is predicted to result in protein truncation. In this family several homozygous individuals showed variable disease manifestations.Conclusion: Molecular test helped in confirmation of the clinical diagnosis and in providing better management of the affected family members, which in turn could significantly improve overall quality of their life. Consequently, preimplantation genetic diagnosis, which is the most acceptable procedure in the Islamic countries, was offered to the heterozygous-carrier couple in order to prevent recurrence of the disease in their future generations.Ó 2014 Production and hosting by Elsevier B.V. on behalf of Ain Shams University.

De novo and recessive forms of congenital heart disease have distinct genetic and phenotypic landscapes

“…Previous studies have linked human ciliopathies to heterotaxy, and several studies have characterized CHD in a subset of those individuals 11,24,25 . Very recently, WES analysis of unrelated laterality patients with CHD identified inherited variation, including low-frequency recessive and compound heterozygous genotypes, as likely candidates for the disease 7 .…”

The impact of primary ciliary dyskinesia on female and male fertility: a narrative review

“…Seventy-one women were subfertile ( Afzelius et al , 1978 ; Zhao et al , 2021 ; Afzelius and Eliasson, 1983 ; McComb et al , 1986 ; Greenstone et al , 1988 ; Lurie et al , 1989 ; Marchini et al , 1992 ; Halbert et al , 1997 ; Lin et al , 1998 ; McLean and Claman, 2000 ; Noone et al , 2004 ; Gavai et al , 2007 ; Ott et al , 2007 ; Abu-Musa et al , 2008 ; Plesec et al , 2008 ; Mishra et al , 2012 ; Chen et al , 2014 ; Onoufriadis et al , 2014 ; Imtiaz et al , 2015 ; Cao et al, 2016 ; Vanaken et al , 2017 ; Höben et al , 2018 ; Yang et al , 2018 ; Zhang et al , 2018 ; Yiallouros et al , 2019 ; Zhou et al , 2020 ; Akbarian et al , 2021 ; De Jesus-Rojas et al , 2021 ; Lu et al , 2021 ; Ma et al , 2021 ; Wang et al , 2021 ). Forty-eight women reported natural pregnancy ( Afzelius et al , 1978 ; Afzelius and Eliasson, 1983 ; Greenstone et al , 1988 ; Eliyahu and Shalev, 1996 ; Noone et al , 2004 ; Blyth and Wellesley, 2008 ; Onoufriadis et al , 2013 ; Marafie et al , 2015 ; Raidt et al , 2015 ; Cao et al, 2016 ; Cooley et al , 2016 ; Vanaken et al , 2017 ; Yiallouros et al , 2019 ;…”