Central Africa; Dysmorphism; KLHL7; PERCHING syndrome; WGS; Genetics; Genetics (clinical)
Abstract :
[en] PERCHING syndrome is a rare multisystem developmental disorder caused by autosomal recessive (AR) variants (truncating and missense) in the Kelch-like family member 7 gene (KLHL7). We report the first phenotypic and molecular description of PERCHING syndrome in a patient from Central Africa. The patient presented multiple dysmorphic features in addition to neurological, respiratory, gastroenteric, and dysautonomic disorders. Clinical Whole Genome Sequencing in the proband and his mother identified two novel heterozygous variants in the KLHL7 gene, including a maternally inherited intronic variant (NM_001031710.2:c.793 + 5G > C) classified as Variant of Uncertain Significance and a frameshift stop gain variant (NM_001031710.2:c.944delG; p.Ser315ThrfsTer23) of unknown inheritance classified as likely pathogenic. Although the diagnosis was only evoked after genomic testing, the review of published patients suggests that this disease could be clinically recognizable and maybe considered as an encephalopathy. Our report will allow expanding the phenotypic and molecular spectrum of Perching syndrome.
Disciplines :
Genetics & genetic processes
Author, co-author :
Makay, Prince ; Centre for Human Genetics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo ; Department of Pediatrics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo ; Centre for Human Genetics, University Hospital, University of Leuven, Leuven, Belgium
Mubungu, Gerrye ; Centre for Human Genetics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo ; Department of Pediatrics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo ; Centre for Human Genetics, University Hospital, University of Leuven, Leuven, Belgium
Mupuala, Aimée; Department of Pediatrics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
Bluske, Krista; Illumina Inc, San Diego, California, USA
Brown, Carolyn; Illumina Inc, San Diego, California, USA
Schmidt, Sarah A; Illumina Inc, San Diego, California, USA
Ngole, Mamy; Centre for Human Genetics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
Fuanani, Patrick; Centre for Human Genetics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo ; Department of Pediatrics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
Perry, Denise L; Illumina Inc, San Diego, California, USA
Lukusa, Prosper; Centre for Human Genetics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo ; Department of Pediatrics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo ; Centre for Human Genetics, University Hospital, University of Leuven, Leuven, Belgium
Devriendt, Koenraad; Centre for Human Genetics, University Hospital, University of Leuven, Leuven, Belgium
Taft, Ryan J; Illumina Inc, San Diego, California, USA
Lumaka, Aimé ; Centre for Human Genetics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo ; Department of Pediatrics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo ; Laboratoire de Génétique Humaine, GIGA-Research Institute, University of Liège, Liège, Belgium
Lumaka Zola, Aimé ; Centre Hospitalier Universitaire de Liège - CHU ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique humaine ; Université de Liège - ULiège > GIGA > GIGA Cancer - Human Genetics
iHope Program, Illumina. VLIR‐UOS Global Mind Program, Grant/Award Number: K210115 and V405213N. Liège University, Grant from the Région Wallonne: RWAL1710180 (WALGEMED). Funding information
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