Whole exome sequencing in three families segregating a pediatric case of sarcoidosis

Calender, Alain; Rollat Farnier, Pierre Antoine; Buisson, Adrien; Pinson, Stéphane; Bentaher, Abderrazzaq; Lebecque, Serge; Corvol, Harriet; Abou Taam, Rola; Houdouin, Véronique; Bardel, Claire; Roy, Pascal; Devouassoux, Gilles; Cottin, Vincent; Seve, Pascal; Bernaudin, Jean-François; Lim, Clarice X.; Weichhart, Thomas; Valeyre, Dominique; Pacheco, Yves; Clement, Annick; Nathan, Nadia

doi:10.1186/s12920-018-0338-x

BMC Medical Genomics

Table 3 Functional summary on genes sharing variants in at least two trios

From: Whole exome sequencing in three families segregating a pediatric case of sarcoidosis

Functional pathways	Genes	Description / Interaction	Function	Related diseases	Add REF
Autophagy and trafficking	Sec16A	Endoplasmic Reticulum Export Factor	ULK1, ULK2 (autophagy initiation)	Familial axial spondyloarthritis	[35, 36, 66]
	AP5B1	Adaptator protein complex 5	AP membrane coat adaptor complex	Atopic march and psoriasis	[37, 67, 68]
	RREB-1	Ras responsive element binding 1	RalA and RalB GTPases, DNA transcriptional regulator	Unknown	[49, 69,70,71]
	ASPN	Asporin (PLAP-1), ligand of CD44	Regulation of TLR2 and TLR4 in macrophages	Osteoarthritis susceptibility	[72,73,74,75]
	RHBDL2	Rhomboid-like-2 serine protease	Regulation of EGFR and anoikis resistance, angiogenesis	Unknown	[76,77,78]
	RHBG	Rhesus-associated (Rh) glycoproteins	Ammonium transport in epithelial cells	Unknown	[79, 80]
	KIR3DL1	killer cell immunoglobulin like receptor	HLA interaction on NK and T-cells	Psoriasis, spondyloarthritis, Behçet	[81,82,83]
	TDRD5	Tudor domain containing 5	Cytoplasmic RNA processing	Spermatogenesis defects	[84, 85]
	MARCH10	Membrane-associated RING-CH 10	Microtubule-associated E3 ubiquitin ligase	Unknown	[86, 87]
	AFAP1	Actin filament associated protein 1	Actin-binding protein and a cSrc-activating protein	Unknown	[88,89,90]
G-proteins regulation	OBSCN	Obscurin	Rho-guanine nucleotide exchange factor	Dilated cardiomyopathies	[91, 92]
	DNAH11	Dynein axonemal heavy chain 11	Component of the ciliary structure	Primary ciliary dyskinesia	[93,94,95]
	CTNND2	δ-catenin/NPRAP/Neurojungin	Regulation of Rho-GTPases in cytoskeleton	Autism, complex human disorders^a	[47, 96]
	CNGB1 (GARP)	Cyclic nucleotide gated channel beta 1	cGMP signaling, guanylate cyclase, expressed on T-reg	Retinitis pigmentosa	[97,98,99,100]
	ADGRV1	Adhesion G protein-coupled receptor V1	G-protein coupled receptor binding calcium	Usher syndrome type II^b	[101, 102]
	NPHS2	Podocin (specific for podocytes)	Filtration barrier in mammalian kidney (TRPC channel)	Nephrotic syndromes	[103,104,105]
T-cell activation	IDO2	Indoleamine 2,3-dioxygenase 2	Acts for IDO1 dependent induction of T-regulatory cells	Colitis, arthritis	[52, 53, 106]
	IGSF3 (EWI-3)	Immunoglobulin superfamily member 3	Putative interaction with CD9 and CD81 (TPSPAN)	Unknown	[107,108,109,110]
	PIEZO1	Piezo type mechanosensitive ion channel 1	Mechanotransduction and regulation of cell morphology	Hereditary Xerocytosis	[111,112,113]
	HSD17B4	Hydroxysteroid 17-beta dehydrogenase 4	Beta-oxidation of very long chain fatty acids	PERRAULT syndrome^c	[114, 115]
Cell cycle - immune synapse	SPICE1	Spindle and centriole associated protein 1	Regulation of centrioles elongation with CEP120 and CPAP	Unknown	[61, 116]
	KNL1 (CASC5)	Kinetochore scaffold 1	Stabilization of sister chromatids to microtubules	Unknown	[64, 117,118,119]
	CCT6B	Chaperonin containing TCP1 subunit 6B	Transcriptional response to stress in mitotic cells	Unknown	[120, 121]
	PCNT	Pericentrin, phosphorylated by PLK1	Ensure proper centrosome and mitotic spindle formation	Primordial dwarfism	[122,123,124]
	PCDHB16	Protocadherin beta 16	Cell-cell adhesion and intracellular signalling	Unknown	[125, 126]
	CMYA5 (TRIM76)	Cardiomyopathy associated 5, myospryn	Muscle target gene for the MEF2A transcription factor	Hypertrophic cardiomyopathy^d,e	[127,128,129,130]
Innate immunity	CPAMD8	Alpha-2-macroglobulin domain containing 8	Up-regulated in immune stimulated cells	Anterior segment dysgenesis	[131, 132]
	WFDC3 (WAP14)	WAP four-disulfide core domain 3	Antimicrobial, immune, and tissue homoeostasis activities	Unknown	[133, 134]
	FCGBP	Fc fragment of IgG binding protein	Regulator of TGF-1-induced EM^f transition	Unknown	[135, 136]

Unclassified: OR11G2, PRSS48, ZNF804A, ZNF717, TYR, SLC16A8, PRSS55, AIM1L
Abbreviations of each gene name are detailed in the text
^athe CTNND2 gene has been linked to a broad spectrum of human diseases, such as cancer, bipolar disorder, schizophrenia, autism, Cri-du-chat syndrome, myopia, cortical cataract-linked Alzheimer’s disease, and infectious diseases. ^bGlycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine rich repeats (LRR), has been found to be highly expressed on the surface of activated T-reg cells. ^cPatients with Usher syndrome type 2 present hearing loss and develop a visual impairment called Retinitis pigmentosa, a disease not observed in our cases, the c.6695A > G variant described in T1 + T2 being not described in this syndrome. ^dPERRAULT syndrome is a rare recessive disease characterized by hearing loss, ovarian dysgenesis, intellectual disability and ataxia, a condition which is not observed in our cases, the c.1606 T > C (T2) and c.392G > A (T3) variants being not linked to this rare disease. ^ethe clinical screening of T1 and T2 affected children did not identify hypertrophic cardiomyopathy. ^fEM: epithelial to mesenchymal transition

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ISSN: 1755-8794

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