Whole exome sequencing identifies TRIOBP pathogenic variants as a cause of post-lingual bilateral moderate-to-severe sensorineural hearing loss

Pollak, Agnieszka; Lechowicz, Urszula; Murcia Pieńkowski, Victor Abel; Stawiński, Piotr; Kosińska, Joanna; Skarżyński, Henryk; Ołdak, Monika; Płoski, Rafał

doi:10.1186/s12881-017-0499-z

Table 1 Mutations in the TRIOBP gene (NM_001039141.2, NP_001034230.1) according to The Human Gene Mutation Database (HGMD), their frequency in ExAC and Polish in-house WES database and available clinical data

From: Whole exome sequencing identifies TRIOBP pathogenic variants as a cause of post-lingual bilateral moderate-to-severe sensorineural hearing loss

variant	phenotype	ExAC allele count	ExAC allele frequency	Pol_Exome allele count	Pol_Exome allele frequency	reference	age of onset	HI level	ethnicity	pathogenicity of variant^d
c.154G>A (p.Asp52Asn)	deafness	23/117210	0,0001962	0	0	[ 17 ]	late onset^a	nd	Japanese	likely pathogenic (PM2)
c.802_805delCAGG (p.Gln268fs)	postlingual hearing loss	1/120722	0,000008283	2	0,0019	this study	postlingual	moderate-to-severe	Polish	pathogenic (PVS1)
c.889C>T (p.Gln297^*a)	deafness non-syndromic	0^c	0^c	0	0	[ 5 ]	prelingual	severe-to-profound	Indian	pathogenic (PVS1)
c.1039C>T (p.Arg347^*a)	deafness non-syndromic	5/120762	0,0000414	0	0	[ 6 ]	prelingual	profound	Palestinian	pathogenic (PVS1)
c.1741C>T (p.Gln581^*a)	deafness non-syndromic	0^c	0^c	0	0	[ 6 ]	prelingual	profound	Palestinian	pathogenic (PVS1)
c.2355_2356delAG (p.Arg785fs)	Hearing loss non-syndromic autosomal recessive	0^c	0^c	0	0	[ 2 ]	nd	nd	Turkish	pathogenic (PVS1)
c.2362C>T (p.Arg788^*a)	deafness non-syndromic	4/120766	0,00003312	0	0	[ 5 ]	prelingual	severe-to-profound	Pakistani	pathogenic (PVS1)
c.2581C>T (p.Arg861^*a)	hearing loss non-syndromic autosomal recessive	1/120758	0,000008281	0	0	[ 31 ]	congenital	profound	Chinese	pathogenic (PVS1)
c.2653del (p.Arg885fs)	hearing loss	0^c	0^c	0	0	[ 9 ]	prelingual	moderate	Dutch	pathogenic (PVS1)
c.2758C>T (p.Arg920^*a)	Hearing loss non-syndromic autosomal recessive	0^c	0^c	0	0	[ 31 ]	congenital	profound	Chinese	pathogenic (PVS1)
c.2992G>A (p.Ala998Thr)	hearing loss	85/120672	0,0007044	0	0	[ 18 ]	congenital	mild to moderate	unknown	likely pathogenic (PM2)
c.3055G>A (p.Gly1019Arg)	deafness non-syndromic	0^c	0^c	0	0	[ 6 ]	prelingual	profound	Palestinian	likely pathogenic (PM2)
c.3202_3203delCG (p.Asp1069fs)	deafness non-syndromic	0^c	0^c	0	0	[ 5 ]	prelingual	severe-to-profound	Indian	pathogenic (PVS1)
c.3202C>T (p.Arg1068^*a)	deafness non-syndromic	1/120342	0,00000831	0	0	[ 5 ]	prelingual	severe-to-profound	Pakistani	pathogenic (PVS1)
c.3232dupC (p.Arg1078fs)	deafness non-syndromic	0^c	0^c	0	0	[ 5 ]	prelingual	severe-to-profound	Indian	pathogenic (PVS1)
c.3232C>T (p.Arg1078Cys)	hearing loss non-syndromic autosomal recessive	355/120198	0,002953	0	0	[ 32 ]	prelingual	nd	Western-European	likely pathogenic (PM2)
c.3349C>T (p.Arg1117*^a)	deafness non-syndromic	0^c	0^c	0	0	[ 5 ]	prelingual	severe-to-profound	Indian	pathogenic (PVS1)
c.3451A>G (p.Met1151Val)	hearing loss non-syndromic autosomal recessive	14/120634	0,0001161	0	0	[ 31 ]	nd	severe to profound HL of the left ear, and mild to moderate HL of the right ear	Chinese	uncertain significance^f
c.3460_3461del (p.Leu1154fs)	hearing loss	5/120614	0,00004145	0	0	[ 9 ]	prelingual	mild	Dutch	pathogenic (PVS1)
c.3662G>A (p.Arg1221Gln)	hearing loss	38/116270	0,0003268	0	0	[ 18 ]	congenital	severe to profound	unknown	uncertain significance^e
c.3942G > C (p.Glu1314Asp)	hearing loss	3/7416	0,0004045	0	0	[ 18 ]	congenital	severe to profound	unknown	uncertain significance^e
c.4187C>T (p.Pro1396Arg)	hearing loss non-syndromic autosomal recessive	1/69904	0,00001431	0	0	[ 31 ]	nd	severe to profound HL of the left ear, and mild to moderate HL of the right ear	Chinese	uncertain significance^f
c.4691G>C (p.Gly1564Ala)	hearing loss	0^c	0^c	0	0	[ 18 ]	nd	Nd	unknown	likely pathogenic (PM2)
c.4840G>T (p.Gly1614Cys)	deafness	18/118002	0,0001525	0	0	[ 17 ]	early onset^b	Nd	Japanese	likely pathogenic (PM2)
c. 5014G>T (p.Gly1672*^a)	postlingual hearing loss	59/103272	0,0005713	4	0,0038	this study/ [9]	postlingual/prelingual	moderate-to-severe/moderate	Polish/Dutch	pathogenic (PVS1)
c.5519G>A (p.Arg1840His)	deafness	3/113104	0,00002652	0	0	[ 17 ]	early onset^b	nd	Japanese	likely pathogenic (PM2)
c.5767G>A (p.Ala1923Thr)	hearing loss	47/31044	0,001514	0	0	[ 18 ]	congenital	mild to moderate	unknown	likely pathogenic (PM2)
c.6362C>T (p.Ser2121Leu)	hearing loss non-syndromic autosomal recessive	56/19236	0,002911	0	0	[ 25 ]	prelingual	nd	Iranian	likely pathogenic (PM2)
c.6736G>A (p.Glu2246Lys)	hearing loss	556/90848	0,00612	0	0	[ 18 ]	congenital	severe to profound	unknown	likely pathogenic (PM2)
c.6860G>A (p.Arg2287His)	deafness	0^c	0^c	0	0	[ 17 ]	early onset^b	nd	Japanese	likely pathogenic (PM2)
c.7000C>T (p.Arg2334Trp)	hearing loss non-syndromic autosomal recessive	2/120504	0,0000166	0	0	[ 32 ]	prelingual	nd	Western-European	likely pathogenic (PM2)

Novel mutation is written in bold
nd no data
^a above 6 y.o
^b below 6 y.o
^cnot reported in ExAC database
^daccording to criteria for classifying pathogenic variants described by Richards et al. [26]; PVS1 - very strong evidence of pathogenicity (null varaints in a gene where loss of function is a known mechanism of disease); PM2 moderate evidence of pathogenicity (absent from controls or at low frequency in ExAC)
^efound in cis with second TRIOBP variant
^f in silico predictions are contradictory

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