Congenital Central Hypoventilation Syndrome malady

NIH Rare Diseases: Congenital central hypoventilation syndrome (CCHS) is a disorder of the autonomic nervous system that causes individuals to hypoventilate (especially during sleep), resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Symptoms usually begin shortly after birth; affected infants hypoventilate upon falling asleep and exhibit a bluish appearance of the skin or lips (cyanosis). Other features may include difficulty regulating heart rate and blood pressure; decreased perception of pain; low body temperature; occasional episodes of profuse sweating; Hirschsprung disease; learning difficulties; eye abnormalities; and a characteristic appearance with a short, wide, somewhat flattened face. It is caused by mutations in the PHOX2B gene and is inherited in an autosomal dominant manner, but over 90 percent of cases result from new mutations and occur in people with no history of the disorder in their family. Treatment typically includes mechanical ventilation or use of a diaphragm pacemaker.³⁰

MalaCards: Congenital Central Hypoventilation Syndrome, also known as CCHS, is related to haddad syndrome and central hypoventilation syndrome. An important gene associated with Congenital Central Hypoventilation Syndrome is ASCL1 (achaete-scute complex homolog 1 (Drosophila)), and among its related pathways are G alpha (q) signalling events and G-protein signaling H-RAS regulation pathway. The compounds lysine and bq 788 sodium salt have been mentioned in the context of this disorder. Affiliated tissues include brain, skin and heart, and related mouse phenotypes are pigmentation and no phenotypic analysis.

Genetics Home Reference: Congenital central hypoventilation syndrome (CCHS) is a disorder that affects breathing. People with this disorder take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Ordinarily, the part of the nervous system that controls involuntary body processes (autonomic nervous system) would react to such an imbalance by stimulating the individual to breathe more deeply or wake up. This reaction is impaired in people with CCHS, and they must be supported with a machine to help them breathe (mechanical ventilation) or a device that stimulates a normal breathing pattern (diaphragm pacemaker). Some affected individuals need this support 24 hours a day, while others need it only at night.¹⁷

Wikipedia: Ondine\'s curse, also called congenital central hypoventilation syndrome (CCHS) or primary alveolar...⁴⁴ more...

OMIM: 209880

GeneReviews summary for ondine

congenital central hypoventilation syndrome 15 30 16 17 cchs 30 16 17 central hypoventilation syndrome, congenital 33 32 ondine-hirschsprung disease 17 43 haddad syndrome 17 43 ondine curse 30 16 idiopathic congenital central alveolar hypoventilation 30 congenital failure of autonomic control 30

congenital central hypoventilation 43 sleep-related respiratory failure 43 primary alveolar hypoventilation 30 hypoventilation syndrome 43 congenital ondine curse 30 sleep apnea, central 43 ondine syndrome 17 ondine's curse 30

Diseases related to congenital central hypoventilation syndrome by text searches and GeneDecks gene sharing:

(show top 50)    (show all 68)

id	Related Disease	Score	Top Affiliating Genes
1	haddad syndrome	31.2	PHOX2B, ASCL1
2	central hypoventilation syndrome	31.1	RET, BDNF, ASCL1, GRP, EN1, PHOX2A
3	hirschsprung's disease	29.0	GDNF, GFRA1, EDNRB, EDN3, PHOX2B, GRP
4	sudden infant death syndrome	28.5	TLX3, PHOX2B, PHOX2A, EN1, GRP, ASCL1
5	apnea	28.1	GDNF, EDN3, PHOX2B, ASCL1, BDNF, RET
6	cerebritis	28.1	GDNF, EDNRB, EDN3, PHOX2B, ASCL1, BDNF
7	neuronitis	23.8	GDNF, TLX3, TLX1, GFRA1, EDNRB, EDN3
8	exotropia	13.3	PHOX2B, PHOX2A
9	waardenburg syndrome type 4	13.1	EDNRB, EDN3
10	waardenburg syndrome type 2	13.0	EDN3, EDNRB
11	megacolon	13.0	EDN3, EDNRB
12	medullary sponge kidney	12.8	RET, GDNF
13	familial medullary thyroid carcinoma	12.8	GDNF, RET
14	sacrococcygeal teratoma	12.7	GDNF, RET
15	pulmonary neuroendocrine tumor	12.7	GRP, ASCL1
16	shah-waardenburg syndrome	12.7	RET, EDN3, EDNRB
17	colonic aganglionosis	12.7	EDNRB, EDN3, RET
18	intestinal pseudo-obstruction	12.7	EDNRB, EDN3, RET
19	waardenburg's syndrome	12.7	RET, EDN3, EDNRB
20	differentiating neuroblastoma	12.6	RET, BDNF, ASCL1
21	carcinoid syndrome	12.6	GRP, ASCL1, RET
22	neuroepithelioma	12.5	EDN3, GRP, RET
23	carcinoid tumors	12.5	GRP, ASCL1, RET
24	developmental disabilities	12.5	RET, BDNF, EDNRB
25	paraganglioma	12.3	EDN3, GRP, ASCL1, RET
26	achalasia	12.3	GDNF, GRP, RET
27	dry eye syndrome	12.2	BDNF, GDNF
28	neuroectodermal tumors	12.2	ASCL1, GRP, GDNF
29	intestinal obstruction	12.1	GDNF, EDNRB, EDN3, RET
30	small-cell cancer of lung	12.1	GDNF, EDNRB, GRP, ASCL1
31	thyroid medullary carcinoma	12.1	GFRA1, GRP, RET
32	multiple endocrine neoplasia type 2a	12.0	RET, GFRA1, GDNF
33	renal agenesis	12.0	RET, GFRA1, GDNF
34	cervical carcinoma	11.9	EDNRB, EDN3, GRP, ASCL1
35	constipation	11.9	GDNF, EDNRB, GRP, RET
36	teratoma	11.9	GDNF, GFRA1, RET
37	wilms tumor	11.9	RET, BDNF, EDN3, GDNF
38	bartter disease	11.9	EDNRB, EDN3, GRP, RET
39	multiple endocrine neoplasia	11.8	RET, GFRA1, GDNF
40	glaucoma	11.8	GDNF, EDNRB, BDNF, RET
41	lung carcinoma	11.6	EDNRB, EDN3, GRP, ASCL1, RET
42	pituitary adenoma	11.5	RET, EDN3, GFRA1, GDNF
43	motor neuron disease	11.5	GDNF, GFRA1, BDNF, RET
44	sleep apnea	11.5	GDNF, EDN3, PHOX2B, ASCL1, BDNF, RET
45	thyroid cancer	11.4	GDNF, GFRA1, ASCL1, RET
46	neuroendocrine tumor	11.2	GDNF, GFRA1, GRP, ASCL1, RET
47	hypertension	11.2	EDNRB, EDN3, PHOX2A, GRP, BDNF, RET
48	thyroid carcinoma	11.2	GDNF, GFRA1, GRP, ASCL1, RET
49	cervicitis	11.2	EDNRB, EDN3, GRP, ASCL1, BDNF, RET
50	astrocytoma	11.0	GDNF, EDNRB, EDN3, EN1, GRP, ASCL1

Clinical features from OMIM: 209880

Approved drugs:

Drug clinical trials:

Genetic tests related to congenital central hypoventilation syndrome:

id	Genetic test	Affiliating Genes
1	Congenital Central Hypoventilation Syndrome clinical/research	PHOX2B

MalaCards organs/tissues related to congenital central hypoventilation syndrome:

²²

MGI Mouse Phenotypes related to congenital central hypoventilation syndrome:

²⁵ (show all 12)

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	pigmentation phenotype	MP:0001186	9.1	ASCL1, EN1, EDN3, EDNRB
2	no phenotypic analysis	MP:0003012	8.6	RET, BDNF, PHOX2A, EDNRB, ASCL1
3	respiratory system phenotype	MP:0005388	8.2	EDNRB, PHOX2B, ASCL1, BDNF, RET, PHOX2A
4	embryogenesis phenotype	MP:0005380	7.6	TLX1, RET, EN1, EDN3, EDNRB, GFRA1
5	normal phenotype	MP:0002873	7.6	PHOX2B, EN1, ASCL1, BDNF, RET, GFRA1
6	integument phenotype	MP:0010771	7.5	BDNF, TLX3, GFRA1, EDN3, EN1, ASCL1
7	growth/size phenotype	MP:0005378	7.3	GDNF, PHOX2B, PHOX2A, EN1, ASCL1, BDNF
8	digestive/alimentary phenotype	MP:0005381	7.1	TLX3, RET, BDNF, EDN3, GDNF, EDNRB
9	mortality/aging	MP:0010768	7.1	EN1, BDNF, RET, PHOX2B, GDNF, TLX3
10	cellular phenotype	MP:0005384	6.9	EDNRB, TLX1, GFRA1, PHOX2B, PHOX2A, ASCL1
11	behavior/neurological phenotype	MP:0005386	6.9	GDNF, EDNRB, PHOX2A, ASCL1, PHOX2B, BDNF
12	nervous system phenotype	MP:0003631	5.8	GFRA1, ASCL1, EN1, PHOX2A, PHOX2B, EDN3

Articles related to congenital central hypoventilation syndrome:

(show all 40)

id	Title	Authors	Year	Affiliating Genes
1	Polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome: rs17884724:A>C is associated with 7-alanine expan sion. (19881470)	Arai H.... Hayasaka K.	2010	PHOX2B
2	Congenital central hypoventilation syndrome and the P HOX2B gene: a model of respiratory and autonomic dysregulation. (20601214)	Patwari P.P.... Weese-Mayer D.E.	2010	PHOX2B
3	Comparison of PHOX2B testing methods in the diagnosis of congenital central hypoventilation syndrome and mosaic carriers. (21051998)	Jennings L.J.... Weese-Mayer D.E.	2010	PHOX2B
4	Cerebral MRI abnormalities in a premature infant with later confirmed congenital central hypoventilation syndrome. (19953265)	van Delft E.... Bambang Oetomo S.	2010	PHOX2B
5	An official ATS clinical policy statement: Congenital central hypoventilation syndrome: genetic basis, diagnosis, and management. (20208042)	Weese-Mayer D.E.... Trang H.	2010	PHOX2B
6	PHOX2B mutation-confirmed congenital central hypoventilation syndrome in a Chinese family: presentation from newborn to adulthood. (19201717)	Lee P.... Wu H.D.	2009	PHOX2B
7	Congenital central hypoventilation syndrome from past to future: model for translational and transitional autonomic medicine. (19422034)	Weese-Mayer D.E.... Ceccherini I.	2009	PHOX2B
8	Congenital Central Hypoventilation Syndrome due to PH OX2b gene defects: inheritance from asymptomatic parents. (19707990)	Hammel M.... Holzinger A.	2009	PHOX2B
9	Congenital Central Hypoventilation syndrome (Ondine's curse): prenatal diagnosis and fetal breathing characteristics. (19784002)	Rajendran G.P.... Manning F.A.	2009	PHOX2B
10	Later-onset congenital central hypoventilation syndrome due to a heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene. (18798833)	Repetto G.M.... Weese-Mayer D.E.	2009	PHOX2B
11	Homozygous mutation of the PHOX2B gene in congenital central hypoventilation syndrome (Ondine's Curse). (18407552)	Trochet D.... Amiel J.	2008	PHOX2B
12	Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for sudden death. (18041756)	Gronli J.O.... Weese-Mayer D.E.	2008	PHOX2B
13	Parental origin and somatic mosaicism of PHOX2B mutations in Congenital Central Hypoventilation Syndrome. (18157832)	Parodi S.... Ceccherini I.	2008	PHOX2B
14	Compound effect of PHOX2B and RET gene variants in congenital central hypoventilation syndrome combined with Hirschsprung disease. (18438890)	Fitze G.... Schackert H.K.	2008	RET, PHOX2B
15	Congenital central hypoventilation syndrome with hyperinsulinism in a preterm infant. (18340402)	Hennewig U.... Hoehn T.	2008	PHOX2B
16	Congenital central hypoventilation syndrome. (17978458)	Samdani P.G.... Goel A.	2007	PHOX2B
17	Congenital central hypoventilation syndrome with PHOX2B gene mutation in a Taiwanese infant. (17282973)	Chen L.R.... Hsieh W.S.	2007	PHOX2B
18	Concomitant existence of total bowel aganglionosis and congenital central hypoventilation syndrome in a neonate with PHOX2B gene mutation. (17270534)	Ou-Yang M.C.... Liu C.A.	2007	PHOX2B
19	Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation-confirmed congenital central hypoventilation syndrome. (17541758)	Diedrich A.... Weese-Mayer D.E.	2007	PHOX2B
20	PHOX2B mutation-confirmed congenital central hypoventilation syndrome: presentation in adulthood. (16873766)	Antic N.A.... Weese-Mayer D.E.	2006	PHOX2B
21	Brainstem anomalies in two patients affected by congenital central hypoventilation syndrome. (16763219)	Bachetti T.... Ottonello G.	2006	PHOX2B
22	Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype. (16888290)	Berry-Kravis E.M.... Weese-Mayer D.E.	2006	PHOX2B
23	Characterization of dermatoglyphics in PHOX2B-confirmed congenital central hypoventilation syndrome. (16882781)	Todd E.S.... Marazita M.L.	2006	PHOX2B
24	Congenital central hypoventilation syndrome and Hirschsprung's disease in an extremely preterm infant. (15930201)	Bajaj R.... Kluckow M.	2005	PHOX2B
25	PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome. (15657873)	Trochet D.... Amiel J.	2005	PHOX2B
26	Distinct pathogenetic mechanisms for PHOX2B associated polyalanine expansions and frameshift mutations in congenital central hypoventilation syndrome. (15888479)	Bachetti T.... Ceccherini I.	2005	PHOX2A
27	The French Congenital Central Hypoventilation Syndrome Registry: general data, phenotype, and genotype. (15653965)	Trang H.... Gaultier C.	2005	PHOX2B
28	Sudden infant death syndrome is not associated with the mutation of PHOX2B gene, a major causative gene of congenital central hypoventilation syndrome. (15185974)	Kijima K.... Hayasaka K.	2004	PHOX2B
29	Haploinsufficiency for Phox2b in mice causes dilated pupils and atrophy of the ciliary ganglion: mechanistic insights into human congenital central hypoventilation syndrome. (15150159)	Cross S.H.... Jackson I.J.	2004	PHOX2B
30	Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. (12640453)	Amiel J.... Lyonnet S.	2003	RET, PHOX2B
31	Association of germline mutations and polymorphisms of the RET proto-oncogene with idiopathic congenital central hypoventilation syndrome in 33 patients. (12566528)	Fitze G.... Schackert H.K.	2003	RET
32	Idiopathic congenital central hypoventilation syndrome: analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2b. (14608649)	Weese-Mayer D.E.... Marazita M.L.	2003	ASCL1, PHOX2B, EN1
33	Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse). (14532329)	de Pontual L.... Amiel J.	2003	ASCL1
34	Molecular analysis of congenital central hypoventilation syndrome. (14566559)	Sasaki A.... Hayasaka K.	2003	RET, BDNF, ASCL1
35	Mutational analysis of the RNX gene in congenital central hypoventilation syndrome. (12407709)	Matera I.... Ceccherini I.	2002	TLX1, TLX3
36	Congenital central hypoventilation syndrome: a novel mutation of the RET gene in an isolated case. (12086152)	Kanai M.... Hayasaka K.	2002	RET
37	Idiopathic congenital central hypoventilation syndrome: evaluation of brain-derived neurotrophic factor genomic DNA sequence variation. (11840487)	Weese-Mayer D.E.... Chakravarti A.	2002	BDNF
38	Congenital central hypoventilation syndrome associated with Hirschsprung's disease: mutation analysis of the RET and endothelin-signaling pathways. (11719874)	Sakai T.... Nirasawa Y.	2001	RET, EDNRB
39	Peripheral chemoreceptors in congenital central hypoventilation syndrome. (9001336)	Cutz E.... Becker L.E.	1997	GRP
40	Endothelin-3 frameshift mutation in congenital central hypoventilation syndrome. (8696331)	Bolk S.... Chakravarti A.	1996	EDN3

Genes related to congenital central hypoventilation syndrome according to GeneCards:

(show all 13)

id	Symbol	Description	Score	GeneCards Section Context
1	ASCL1	achaete-scute complex homolog 1 (Drosophila)	11.1	Publications, Summaries
2	PHOX2B	paired-like homeobox 2b	11.0	Publications
3	PHOX2A	paired-like homeobox 2a	11.0	Publications
4	TLX3	T-cell leukemia homeobox 3	11.0	Publications
5	EN1	engrailed homeobox 1	11.0	Publications
6	TLX1	T-cell leukemia homeobox 1	11.0	Publications
7	EDN3	endothelin 3	11.0	Publications
8	RET	ret proto-oncogene	11.0	Publications
9	EDNRB	endothelin receptor type B	11.0	Publications
10	BDNF	brain-derived neurotrophic factor	11.0	Publications
11	GDNF	glial cell derived neurotrophic factor	11.0
12	GFRA1	GDNF family receptor alpha 1	11.0	Publications
13	GRP	gastrin-releasing peptide	11.0	Publications

Pathways related to congenital central hypoventilation syndrome according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	G alpha (q) signalling events38	9.1	GRP, EDN3, EDNRB
2	G-protein signaling H-RAS regulation pathway10	8.7	RET, GDNF, GFRA1
3	G-protein signaling_H-RAS regulation pathway41	8.6	GDNF, GFRA1, RET
4	Development GDNF family signaling10	8.5	GFRA1, RET, GDNF
5	Development_GDNF family signaling41	8.3	GDNF, GFRA1, RET

Compounds related to congenital central hypoventilation syndrome according to GeneDecks:

(show all 50)

id	Compound	Score	Top Affiliating Genes
1	lysine32	10.2	EDNRB
2	bq 788 sodium salt42	10.1	EDN3, EDNRB
3	bq 302032	10.1	EDN3, EDNRB
4	bq61032	10.1	EDN3, EDNRB
5	pd 14289332	10.1	EDN3, EDNRB
6	sarafotoxin32	10.1	EDN3, EDNRB
7	irl 162032	10.1	EDNRB, EDN3
8	tezosentan32	10.0	EDNRB, EDN3
9	fr13931732	10.0	EDN3, EDNRB
10	bq78832	10.0	EDNRB, EDN3
11	bq12332	10.0	EDNRB, EDN3
12	bosentan32 9 9	12.0	EDNRB, EDN3
13	propargylamine32	9.7	GDNF, BDNF
14	riluzole32 9 9	11.7	GDNF, BDNF
15	dopac32	9.6	BDNF, GDNF
16	rasagiline32 9 9	11.6	BDNF, GDNF
17	phosphoramidon32 9 9	11.6	GRP, EDN3, EDNRB
18	tetrodotoxin32	9.5	BDNF, GRP, EDN3
19	1 methyl 4 phenylpyridinium32	9.4	GDNF, BDNF
20	selegiline32 9 9	11.3	GDNF, BDNF
21	nifedipine32 9 9	11.3	EDN3, GRP, BDNF
22	dbc-amp32	9.3	EDN3, GDNF, BDNF
23	levodopa32 9 9	11.3	EDN3, BDNF, GDNF
24	carbachol32 9 9	11.3	EDN3, GRP, BDNF
25	catecholamine32	9.2	BDNF, RET, GDNF
26	melatonin32 42 9 18 9	13.2	EDNRB, GDNF, BDNF
27	capsaicin32	9.2	GDNF, GRP, BDNF
28	inositol 1,4,5 trisphosphate32	9.1	BDNF, GRP, EDN3
29	cocaine32 9 9	11.0	BDNF, GRP, GDNF
30	indomethacin32 9 9	11.0	GRP, EDN3, BDNF, EDNRB
31	aspartate32	9.0	BDNF, GDNF, EDN3, RET
32	choline32 9 18 9	11.8	BDNF, GDNF, GRP, RET
33	potassium32 9 18 9	11.8	EDN3, EDNRB, GDNF, BDNF
34	thapsigargin32 42	9.8	GRP, BDNF, EDN3
35	wortmannin32 42	9.7	BDNF, RET, GRP, GDNF
36	phosphoinositide32	8.7	EDN3, GDNF, BDNF, GRP
37	bromodeoxyuridine32	8.7	GFRA1, BDNF, GDNF
38	heparan sulfate32 18	9.6	GDNF, GFRA1, RET
39	acetylcholine32 9 18 9	11.4	BDNF, GRP, EDN3, EDNRB, GDNF
40	adenylate32	8.4	EDN3, GDNF, BDNF, EDNRB, GRP
41	alanine32	8.3	EDNRB, GRP, PHOX2B, EDN3, RET, GDNF
42	glutamate32	8.2	BDNF, GRP, EDN3, EDNRB, GDNF
43	cyclic amp32 18	9.2	PHOX2B, RET, GDNF, GRP, EDN3, BDNF
44	retinoic acid32 42 18	10.1	BDNF, RET, ASCL1, GRP, EDNRB, GDNF
45	phosphatidylinositol32	8.0	EDN3, RET, GRP, EDNRB, GDNF, BDNF
46	vegf32	8.0	RET, GDNF, EDNRB, EDN3, GRP, BDNF
47	norepinephrine32 9 18 9	10.9	GDNF, EDNRB, EDN3, PHOX2B, PHOX2A, GRP
48	serine32	7.5	RET, GRP, EDN3, EDNRB, GDNF, BDNF
49	dopamine32 9 18 9	9.9	RET, GDNF, EDN3, PHOX2B, ASCL1, PHOX2A
50	tyrosine32	6.0	RET, BDNF, ASCL1, PHOX2A, PHOX2B, EDN3

Biological processes related to congenital central hypoventilation syndrome according to GeneDecks:

(show all 16)

id	Name	GO ID	Score	Top Affiliating Genes
1	parasympathetic nervous system development	GO:048486	10.2	PHOX2B, PHOX2A
2	noradrenergic neuron differentiation	GO:003357	10.1	PHOX2B, PHOX2A
3	neuron fate specification	GO:048665	10.1	TLX3, ASCL1
4	dopaminergic neuron differentiation	GO:071542	10.1	PHOX2B, PHOX2A
5	regulation of respiratory gaseous exchange by neurological system process	GO:002087	9.9	TLX3, PHOX2B
6	midbrain development	GO:030901	9.9	EN1, PHOX2A
7	vein smooth muscle contraction	GO:014826	9.9	EDNRB, EDN3
8	posterior midgut development	GO:007497	9.9	EDNRB, RET
9	neuron migration	GO:001764	9.8	ASCL1, TLX3, PHOX2B
10	vasoconstriction	GO:042310	9.7	EDNRB, EDN3
11	melanocyte differentiation	GO:030318	9.5	EDNRB, EDN3
12	sympathetic nervous system development	GO:048485	9.3	ASCL1, GDNF, PHOX2B, PHOX2A
13	enteric nervous system development	GO:048484	9.0	EDNRB, RET, PHOX2B, GDNF
14	neural crest cell migration	GO:001755	8.9	RET, GDNF, EDNRB, EDN3
15	positive regulation of transcription from RNA polymerase II promoter	GO:045944	8.7	ASCL1, EN1, PHOX2A, TLX1, GDNF, PHOX2B
16	cell surface receptor signaling pathway	GO:007166	8.5	GFRA1, EDNRB, EDN3

Molecular functions related to congenital central hypoventilation syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	RNA polymerase II regulatory region sequence-specific DNA binding	GO:000977	9.6	PHOX2A, PHOX2B
2	sequence-specific DNA binding	GO:043565	9.3	ASCL1, EN1, TLX1, TLX3
3	sequence-specific DNA binding transcription factor activity	GO:003700	8.7	PHOX2B, ASCL1, EN1, PHOX2A, TLX3, TLX1
4	receptor binding	GO:005102	8.0	GFRA1, GRP, GDNF, EDN3