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Open AccessArticle

Autosomal Dominantly Inherited GREB1L Variants in Individuals with Profound Sensorineural Hearing Impairment

1
Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer’s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
2
Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
3
Department of ENT, St-Augustinus Hospital Antwerp, 2610 Antwerp, Belgium
4
Synthetic Protein Engineering Lab (SPEL), Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea
5
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
6
Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, 2650 Antwerp, Belgium
*
Author to whom correspondence should be addressed.
Genes 2020, 11(6), 687; https://doi.org/10.3390/genes11060687
Received: 1 June 2020 / Revised: 16 June 2020 / Accepted: 20 June 2020 / Published: 23 June 2020
(This article belongs to the Special Issue Genetics of Hearing Impairment)
Congenital hearing impairment is a sensory disorder that is genetically highly heterogeneous. By performing exome sequencing in two families with congenital nonsyndromic profound sensorineural hearing loss (SNHL), we identified autosomal dominantly inherited missense variants [p.(Asn283Ser); p.(Thr116Ile)] in GREB1L, a neural crest regulatory molecule. The p.(Thr116Ile) variant was also associated with bilateral cochlear aplasia and cochlear nerve aplasia upon temporal bone imaging, an ultra-rare phenotype previously seen in patients with de novo GREB1L variants. An important role of GREB1L in normal ear development has also been demonstrated by greb1l−/− zebrafish, which show an abnormal sensory epithelia innervation. Last, we performed a review of all disease-associated variation described in GREB1L, as it has also been implicated in renal, bladder and genital malformations. We show that the spectrum of features associated with GREB1L is broad, variable and with a high level of reduced penetrance, which is typically characteristic of neurocristopathies. So far, seven GREB1L variants (14%) have been associated with ear-related abnormalities. In conclusion, these results show that autosomal dominantly inherited variants in GREB1L cause profound SNHL. Furthermore, we provide an overview of the phenotypic spectrum associated with GREB1L variants and strengthen the evidence of the involvement of GREB1L in human hearing. View Full-Text
Keywords: autosomal dominant inheritance; exome sequencing; GREB1L; profound nonsyndromic hearing impairment; cochlear aplasia; cochlear nerve aplasia; neural crest; neurocristopathy autosomal dominant inheritance; exome sequencing; GREB1L; profound nonsyndromic hearing impairment; cochlear aplasia; cochlear nerve aplasia; neural crest; neurocristopathy
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MDPI and ACS Style

Schrauwen, I.; Liaqat, K.; Schatteman, I.; Bharadwaj, T.; Nasir, A.; Acharya, A.; Ahmad, W.; Van Camp, G.; Leal, S.M. Autosomal Dominantly Inherited GREB1L Variants in Individuals with Profound Sensorineural Hearing Impairment. Genes 2020, 11, 687.

AMA Style

Schrauwen I, Liaqat K, Schatteman I, Bharadwaj T, Nasir A, Acharya A, Ahmad W, Van Camp G, Leal SM. Autosomal Dominantly Inherited GREB1L Variants in Individuals with Profound Sensorineural Hearing Impairment. Genes. 2020; 11(6):687.

Chicago/Turabian Style

Schrauwen, Isabelle; Liaqat, Khurram; Schatteman, Isabelle; Bharadwaj, Thashi; Nasir, Abdul; Acharya, Anushree; Ahmad, Wasim; Van Camp, Guy; Leal, Suzanne M. 2020. "Autosomal Dominantly Inherited GREB1L Variants in Individuals with Profound Sensorineural Hearing Impairment" Genes 11, no. 6: 687.

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