Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease

Lantieri, Francesca; Gimelli, Stefania; Viaggi, Chiara; Stathaki, Elissavet; Malacarne, Michela; Santamaria, Giuseppe; Grossi, Alice; Mosconi, Manuela; Sloan-Béna, Frédérique; Prato, Alessio Pini; Coviello, Domenico; Ceccherini, Isabella

doi:10.1186/s13023-019-1205-3

Orphanet Journal of Rare Diseases

Table 3 Variants selected for validation, results and corresponding samples

From: Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease

variant call	Sample ID	gender	Chromosomal region	Aberr. type	N. probes	size (bp)	validation method	validated	parental origin	RET mutations	RET HSCR risk haplotype	HSCR lenght	syndromic	locus	affected genes (or flanking genes if no gene maps into the region)
variant call	Sample ID	gender	(chr:start-end)	Aberr. type	N. probes	size (bp)	validation method	validated	parental origin	RET mutations	RET HSCR risk haplotype	HSCR lenght	syndromic	locus
1	HSCR000	F	9:110381888–110,401,999	gain	9	20,111	qPCR	Y^c	M	interstitial deletion	unknown	TCA	no	9q31	(KLF4; ACTL7B)
5	HSCR005	M	7:84217007–84,225,649	loss	4	8642	qPCR	Y^d	M	no	homoz.	S	no	SEMA3A/3D	(SEMA3A; SEMA3D)
6	HSCR005	M	10:43679892–43,680,816	loss	5	924	PCR	N	–	no	homoz.	S	no	–	–
8	HSCR006	M	10:43679612–43,680,816	loss	6	1204	PCR	N	–	no	homoz.	L	no	–	–
20^b	HSCR018	M	9:109336464–109,348,467	gain	6	12,003	qPCR	Y	M	p.P399L	wt	L	no	9q31	(TMEM38B; ZNF462)
21	HSCR019	F	1:146638075–147,824,207	loss	4	2,585,968	qPCR	Y^c	M	no	homoz.	S	VSD + mandibular hypoplasia	1q21	PRKAB2, PDIA3P, FMO5, CHD1L, BCL9, ACP6, GJA5, GJA8, GPR89B, GPR89C, PDZK1P1, LOC200030, NBPF11
27^b	HSCR043	M	9:109273643–109,275,694	loss	2	2051	qPCR	Y	M	p.K821Q	homoz.	S	no	9q31	(TMEM38B; ZNF462)
28^b	HSCR045	M	7:84594683–84,607,065^e	loss	6	12,382	qPCR	N	n.a.	no	unknown	L	no	–	–
29^b			8:32597644–32,598,929	loss	3	1285	qPCR	Y						NRG1	NRG1
30			10:43679612–43,680,816	loss	6	1204	PCR	N						–	–
35	HSCR146	M	15:58257674–59,009,890	gain	2	752,216	aCGH 8x60K	Y	M	no	homoz.	S	no	15q21	ALDH1A2, AQP9, LIPC, ADAM10, HSP90AB4P
36	HSCR146	M	19:30888070–30,891,329	gain	2	3259	qPCR	N	–	no	homoz.	S	no	–	–
42	HSCR195	M	9:112078131–112,089,193	loss	5	11,062	qPCR	not conclusive ^c	n.a.	p.E610K	homoz.	S	no	9q31	EPB41L4B
43	HSCR217	M	16:82200334–82,202,467	gain	2	2133	qPCR	Y	de novo	p.R813L	homoz.	S	no	16q23	MPHOSPH6
60	HSCR349	F	10:43573685–43,574,005^e	gain	2	320	qPCR	N	–	no	homoz.	?	no	–	–
61	HSCR374	F	10:43473690–43,474,033^e	gain	4	343	qPCR	N	–	no	homoz.	L	no	–	–
69^c	HSCR403	F	4:41746863–41,751,291	loss	11	4428	qPCR	Y	M	no	homoz.	S	no	PHOX2B	PHOX2B
82	HSCR481	F	19:31954093–31,966,036	loss	5	11,943	qPCR	Y	n.a.	no	unknown	?	Down s.	19q12	(TSHZ3; THEG5)
72^a	HSCR403	F	22:21494163–21,704,972^e	gain	5	210,809		- ^c	–	no	homoz.	S	no	22q11	GGT2, POM121L7

CNVs reported in bold are those confirmed to be true
^a the CNVs reported in the last line was not actually selected for validation and not analyzed for parental origin because considered unlikely at the visual inspection, but lately found confirmed on two replicates and thus included in the present table
^b aberration not detected by the software call, but identified by visual inspection
^c confirmed on an aCGH replicate
^d reported on DGV (freq< 1%)
^e unlikely at the visual inspection
^f compatible with 1q21.1 recurrent microdeletion
n.a. parents not available
VSD VentricularSeptalDefect

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ISSN: 1750-1172

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