Co-occurrence of orofacial clefts and clubfoot phenotypes in a sub-Saharan African cohort: Whole-exome sequencing implicates multiple syndromes and genes.

Autor:	Gowans LJJ; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.; Department of Oral and Maxillofacial Sciences, Dental School, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Al Dhaheri N; Department of Medical Genetics, John Hopkins University, Baltimore, MD, USA., Li M; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Busch T; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Obiri-Yeboah S; Department of Oral and Maxillofacial Sciences, Dental School, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Oti AA; Department of Oral and Maxillofacial Sciences, Dental School, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Sabbah DK; Department of Orthodontics and Child Oral Health, Dental School, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Arthur FKN; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Awotoye WO; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Alade AA; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA., Twumasi P; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Agbenorku P; Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Plange-Rhule G; Department of Child Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Naicker T; Department of Pediatrics, University of KwaZulu-Natal, South Africa., Donkor P; Department of Oral and Maxillofacial Sciences, Dental School, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.; Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Murray JC; Department of Pediatrics, University of Iowa, Iowa City, IA, USA., Sobreira NLM; Department of Medical Genetics, John Hopkins University, Baltimore, MD, USA., Butali A; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA.
Jazyk:	angličtina
Zdroj:	Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2021 Apr; Vol. 9 (4), pp. e1655. Date of Electronic Publication: 2021 Mar 14.
DOI:	10.1002/mgg3.1655
Abstrakt:	Background: Orofacial clefts (OFCs) are congenital malformations of the face and palate, with an incidence of 1 per 700 live births. Clubfoot or congenital talipes equinovarus (CTEV) is a three-dimensional abnormality of the leg, ankle, and feet that leads to the anomalous positioning of foot and ankle joints and has an incidence of 1 per 1000 live births. OFCs and CTEV may occur together or separately in certain genetic syndromes in addition to other congenital abnormalities. Here, we sought to decipher the genetic etiology of OFC and CTEV that occurred together in six probands. Methods: At the time of recruitment, the most clinically obvious congenital anomalies in these individuals were the OFC and CTEV. We carried out whole-exome sequencing (WES) on DNA samples from probands and available parents employing the Agilent SureSelect XT kit and Illumina HiSeq2500 platform, followed by bioinformatics analyses. WES variants were validated by clinical Sanger Sequencing. Results: Of the six probands, we observed probable pathogenic genetic variants in four. In three probands with probable pathogenic genetic variants, each individual had variants in three different genes, whereas one proband had probable pathogenic variant in just one gene. In one proband, we observed variants in DIS3L2, a gene associated with Perlman syndrome. A second proband had variants in EPG5 (associated with Vici Syndrome), BARX1 and MKI67, while another proband had potentially etiologic variants in FRAS1 (associated with Fraser Syndrome 1), TCOF1 (associated with Treacher Collins Syndrome 1) and MKI67. The last proband had variants in FRAS1, PRDM16 (associated with Cardiomyopathy, dilated, 1LL/Left ventricular noncompaction 8) and CHD7 (associated with CHARGE syndrome/Hypogonadotropic hypogonadism 5 with or without anosmia). Conclusion: Our results suggest that clubfoot and OFCs are two congenital abnormalities that can co-occur in certain individuals with varying genetic causes and expressivity, warranting the need for deep phenotyping. (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text ve formátu PDF