Pachyonychia Congenita malady

NIH Rare Diseases: Pachyonychia congenita (PC) is a very rare inherited condition that primarily affects the nails and skin. The fingernails and toenails are usually thickened and abnormally shaped. Affected individuals may also develop painful calluses and blisters on the soles of their feet and palms of their hands (palmoplantar keratoderma). Additional features include white patches on the tongue and inside of the mouth; bumps around the elbows, knees, and waistline; cysts in the armpits, groin, back, or scalp; and excessive sweating on the palms or soles of the feet. Features may vary among affected individuals.Two major types of this condition have been described: pachyonychia congenita type 1 (PC-1) and pachyonychia congenita type 2 (PC-2). PC is caused by a mutation in one of four genes. Mutations in the KRT6A and KRT16 gene cause PC-1; mutations in KRT6B and KRT17 result in PC-2.³⁰

MalaCards: Pachyonychia Congenita, also known as pachyonychia congenita, jadassohn-lewandowsky type, is related to pachyonychia congenita type 2 and steatocystoma multiplex. An important gene associated with Pachyonychia Congenita is KRT6B (keratin 6B), and among its related pathways are Cytoskeletal Signaling and Cytoskeleton remodeling Keratin filaments. The compounds acitretin and dithranol have been mentioned in the context of this disorder. Affiliated tissues include skin and tongue, and related mouse phenotypes are digestive/alimentary and integument.

Genetics Home Reference: Pachyonychia congenita is a condition that primarily affects the nails and skin. The signs and symptoms of this condition usually become apparent within the first few months of life, although a rare form of the condition known as pachyonychia congenita tarda appears in adolescence or early adulthood.¹⁷

Wikipedia: Pachyonychia congenita is an autosomal dominant skin disorder.⁴⁴ more...

OMIM: 167200

GeneReviews summary for pc

Aliases & Descriptions:

pachyonychia congenita 6 7 15 30 17 8 43 pachyonychia congenita, jadassohn-lewandowsky type 6 33 pachyonychia congenita syndrome 30 16 pachyonychia congenita type 1 6 30 congenital pachyonychia 30 17 pachyonychia congenita, jadassohn lewandowsky type 43 pachyonychia congenita jadassohn lewandowsky type 30 jackson-lawler type pachyonychia congenita 6

pachyonychia congenita, type 2 (disorder) 43 jadassohn-lewandowski syndrome (pc-1) 17 jackson-lawler syndrome (pc-2) 17 jadassohn-lewandowsky syndrome 6 jadassohn lewandowsky syndrome 30 pachyonychia congenita, type 1 32 lewandowski kikolich syndrome 30 pc1 30

Disease types for pachyonychia congenita family:

pachyonychia congenita type 2

Diseases related to pachyonychia congenita by text searches and GeneDecks gene sharing:

(show top 50)    (show all 227)

id	Related Disease	Score	Top Affiliating Genes
1	pachyonychia congenita type 2	36.2	KRT6B, KRT17
2	steatocystoma multiplex	32.9	KRT16, KRT17
3	median rhomboid glossitis	30.2	KRT6A, KRT6B
4	glossitis	30.1	KRT6A, KRT6B
5	focal palmoplantar keratoderma	29.9	KRT6C, KRT16
6	keratitis	29.0	GJB6, KRT16, KRT17, KRT6B
7	carcinoma	28.8	KRT2, KRT9, KRT6B, KRT17, KRT6A, KRT81
8	keratoderma	25.2	KRTAP11-1, KRT9, KRT6C, KRT6B, KRT17, KRT6A
9	primary cutaneous amyloidosis	13.2	KRT5, KRT17
10	hair disease	13.1	KRT86, KRT81
11	exfoliative ichthyosis	13.1	KRT5, KRT2
12	nonepidermolytic palmoplantar keratoderma	13.1	KRTAP11-1, KRT16
13	epidermolytic palmoplantar keratoderma	13.0	KRT9, KRT16
14	triple-a syndrome	12.9	KRT86, KRT81
15	skin disease	12.9	KRT6A, KRT6B, KRT9
16	epidermolytic hyperkeratosis	12.7	FLG, KRT5
17	hereditary mucosal leukokeratosis	12.6	KRTAP11-1, KRT2, KRT6A, KRT86
18	palmoplantar keratosis	12.6	KRT9, KRT17, KRT16, KRT5
19	basal cell carcinoma	12.6	KRT17, KRT86, KRT16, KRT5
20	bowen syndrome	12.6	KRT17, KRT16, FLG
21	nail disease	12.6	KRT6B, KRT6A, KRT81, PCSK5
22	keratoacanthoma	12.5	KRT17, KRT16, FLG
23	x-linked ichthyosis	12.5	KRT86, FLG
24	contact dermatitis	12.5	KRT17, KRT16, FLG
25	molluscum contagiosum	12.3	KRT16, FLG
26	ectodermal dysplasia	12.3	GJB6, KRT16, KRT6A, KRT17, KRT6B
27	congenital ichthyosiform erythroderma	12.3	FLG, KRT2
28	nevus	12.3	FLG, KRT5, KRT16, KRT17
29	acne	12.2	KRT17, KRT16, FLG
30	amyloidosis	12.1	PCSK5, KRT5, KRT17
31	prostatitis	12.1
32	alopecia	12.1	FLG, KRT16, KRT86, KRT81
33	papilloma	12.1	FLG, KRT5, KRTAP11-1
34	cholesteatoma	12.0	FLG, GJB6, KRT16
35	mayer-rokitansky-kuster-hauser syndrome	11.8	FLG, KRT5, KRT16, KRT6A, KRT17, KRT6B
36	prostate cancer	11.7
37	epidermolysis bullosa	11.4	KRT2, KRT9, KRT17, KRT6A, KRT5, FLG
38	monilethrix	11.1	KRT16, KRT86, KRT81, KRTAP11-1, KRT2, KRT9
39	pharyngitis	11.0	KRT2, KRT6C, KRT72, KRT6B, KRT6A, KRT81
40	neuronitis	10.9
41	ichthyosis	10.5	KRT2, KRT9, KRT17, KRT86, KRT16, KRT5
42	pheochromocytoma	10.3
43	epidermolysis bullosa simplex	10.0	FLG, KRTAP11-1, KRT2, KRT9, KRT6B, KRT17
44	keratosis	9.9	KRT9, KRT6C, KRT6B, KRT17, KRT6A, KRT81
45	prostate carcinoma	9.2
46	insulin resistance	8.7
47	krt16-related pachyonychia congenita	8.2
48	krt17-related pachyonychia congenita	8.2
49	krt6a-related pachyonychia congenita	8.2
50	krt6b-related pachyonychia congenita	8.2

Clinical features from OMIM: 167200

Approved drugs:

Drug clinical trials:

MalaCards organs/tissues related to pachyonychia congenita:

²²

MGI Mouse Phenotypes related to pachyonychia congenita:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	digestive/alimentary phenotype	MP:0005381	8.7	PCSK5, KRT5, KRT16, KRT6A, KRT17, KRT6B
2	integument phenotype	MP:0010771	7.8	KRT2, KRT6B, KRT17, KRT6A, KRT16, KRT5
3	craniofacial phenotype	MP:0005382	7.4	PCSK5, KRT2, KRT6B, KRT17, KRT6A, KRT16

Articles related to pachyonychia congenita:

(show all 48)

id	Title	Authors	Year	Affiliating Genes
1	Keratin 17 mutation in pachyonychia congenita type 2 in a Chinese Han family]. (21287500)	Zhang S.D.... Zhao J.J.	2011	KRT17
2	Pachyonychia congenita with laryngeal obstruction. (21554383)	Haber R.M.... Drummond D.	2011	KRT6A
3	The 521 T--> C mutation in the keratin 6A gene in a pedigree with pachyonychia congenita type I (20140871)	Yang L.... Ni J.	2010	KRT6A
4	Novel and recurrent keratin 6A (KRT6A) mutations in C hinese patients with pachyonychia congenita type 1. (19416275)	Lv Y.M.... Zhang X.J.	2009	KRT6A
5	Pachyonychia congenita type 2, N92S mutation of kerat in 17 gene: clinical features, mutation analysis and pathological view. (19107515)	Cogulu O.... Ozkinay F.	2009	KRT17, KRT6B
6	Increased pachyonychia congenita severity in patients with concurrent keratin and filaggrin mutations. (19785597)	Gruber R.... Schmuth M.	2009	KRT17, KRT16, FLG
7	Rapamycin selectively inhibits expression of an induc ible keratin (K6a) in human keratinocytes and improves symptoms in pachyonychia congenita patients. (19699613)	Hickerson R.P.... Kaspar R.L.	2009	KRT17, KRT6A, KRT16
8	Two mutations of the KRT6A gene in Chinese patients with pachyonychia congenita type I (19806570)	Bai Z.L.... He D.L.	2009	KRT6A, KRT16
9	Pachyonychia congenita: a case report. (20099620)	Kohli N.	2009	KRT6A, KRT16, KRT6B
10	Development of therapeutic siRNAs for pachyonychia congenita. (17762855)	Smith F.J.... McLean W.H.	2008	KRT6A
11	Therapeutic interference: a step closer for pachyonychia congenita? (18071332)	Rugg E.L.	2008	KRT6A
12	Recurrent mutation in keratin 17 in a large family with pachyonychia congenita type 2. (18347808)	Oh Adib C.... Leachman S.	2008	KRT17, KRTAP17-1
13	Mutations of KRT6A are more frequent than those of KRT16 in pachyonychia congenita type 1: report of a novel and a recently reported mutation in two unrelated Chinese families. (18489596)	Bai Z.L.... Kang R.H.	2008	KRT16, KRT6A
14	A novel point mutation of keratin 17 (KRT17) in a Japanese family with pachyonychia congenita type 2: an RNA-based genetic analysis using a single hair bulb. (18547302)	Tsuda T.... Yamanishi K.	2008	KRT17
15	A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita. (17719747)	Liao H.... Smith F.J.	2007	KRT17, KRT16, KRT6A
16	A novel missense mutation L468Q of keratin 6a in pachyonychia congenita type 1. (17309457)	Zhou H.L.... Zhang X.J.	2007	KRT6A
17	Pachyonychia congenita associated with median rhomboid glossitis. (17511954)	Karen J.K.... Schaffer J.V.	2007	KRT6A, KRT6B
18	Keratin 17 mutation in pachyonychia congenita type 2 patient with early onset steatocystoma multiplex and Hutchinson-like tooth deformity. (16620218)	Oh S.-W.... Kim S.-C.	2006	KRT17
19	SiRNA-mediated selective inhibition of mutant keratin mRNAs responsible for the skin disorder pachyonychia congenita. (17145926)	Hickerson R.P.... Kaspar R.L.	2006	KRT6A, KRT6B
20	Mouse models in preclinical studies for pachyonychia congenita. (16250208)	Chen J.... Roop D.R.	2005	KRT17, KRT16, KRT6A
21	Insights into genotype-phenotype correlation in pachyonychia congenita from the human intermediate filament mutation database. (16250207)	McLean W.H.... Cassidy A.J.	2005	KRT6A, KRT6B
22	Clinical and pathological features of pachyonychia congenita. (16250204)	Leachman S.A.... Lane E.B.	2005	KRT6A, KRT6B
23	The genetic basis of pachyonychia congenita. (16250206)	Smith F.J.... McLean W.H.	2005	KRT6A, KRT6B
24	Identification of a recurrent mutation in keratin 17 in a Japanese family with pachyonychia congenita type 2. (15795125)	Uchida T.... Fujimoto W.	2005	KRT17
25	A severe case of pachyonychia congenita type I due to a novel proline mutation in keratin 6a. (15840119)	Garcia-Rio I.... Smith F.J.	2005	KRT6A
26	A novel mutation in the second half of the keratin 17 1A domain in a large pedigree with delayed-onset pachyonychia congenita type 2. (15102078)	Xiao S.-X.... Shi Y.-Z.	2004	KRT5, KRT17
27	A de nono I462S mutation in the KRT6A gene is associated with pachyonychia congenita type I (15387942)	Kang X.J.... Zhang X.	2004	KRT6A
28	Clouston syndrome can mimic pachyonychia congenita. (14708603)	van Steensel M.A.... Smith F.J.	2003	GJB6
29	Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts. (12653736)	Feng Y.G.... Pan M.	2003	KRT17
30	Identification of a recurrent mutation in keratin 6a in a patient with overlapping clinical features of pachyonychia congenita types 1 and 2. (12823309)	Ward K.M.... Celebi J.T.	2003	KRT6A, KRT6B
31	A novel point mutation in the keratin 17 gene in a Japanese case of pachyonychia congenita type 2. (11874497)	Hashiguchi T.... Kanzaki T.	2002	KRT17
32	Novel keratin 17 mutations in pachyonychia congenita type 2. (11348474)	Smith F.J.D.... McLean W.H.I.	2001	KRT17
33	Delayed-onset pachyonychia congenita associated with a novel mutation in the central 2B domain of keratin 16. (11359398)	Connors J.B.... Milstone L.M.	2001	KRT16
34	Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita. (11886499)	Terrinoni A.... McLean W.H.I.	2001	KRT17, KRT6A, KRT16
35	Novel keratin 16 mutations and protein expression studies in pachyonychia congenita type 1 and focal palmoplantar keratoderma. (10839714)	Smith F.J.... McLean W.H.I.	2000	KRT16
36	Keratin 17 expression in the hard epithelial context of the hair and nail, and its relevance for the pachyonychia congenita phenotype. (10844551)	McGowan K.M.... Coulombe P.A.	2000	KRT17
37	Pachyonychia congenita. Keratin gene mutations with pleiotropic effect (10464680)	Swensson O.	1999	KRT6A, KRT6B
38	Mutation report: identification of a germline mutation in keratin 17 in a family with pachyonychia congenita type 2. (10571744)	Celebi J.T.... Peacocke M.	1999	KRT17, KRT6B
39	A mutation detection strategy for the human keratin 6A gene and novel missense mutations in two cases of pachyonychia congenita type 1. (10232400)	Smith F.J.... McLean W.H.	1999	KRT6A
40	Cloning of multiple keratin 16 genes facilitates prenatal diagnosis of pachyonychia congenita type 1. (10521820)	Smith F.J.... McLean W.H.I.	1999	KRT16
41	Novel proline substitution mutations in keratin 16 in two cases of pachyonychia congenita type 1. (10606845)	Smith F.J.D.... McLean W.H.I.	1999	KRT6A, KRT16
42	A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2. (9618173)	Smith F.J.D.... McLean W.H.I.	1998	KRT17, KRT6B
43	Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2. (9767294)	Covello S.P.... McLean W.H.I.	1998	KRT17
44	Pachyonychia congenita type 2: keratin 17 mutation in a Japanese case. (9632020)	Fujimoto W.... Arata J.	1998	KRT17
45	Missense mutations in keratin 17 cause either pachyonychia congenita type 2 or a phenotype resembling steatocystoma multiplex. (9008238)	Smith F.J.D.... McLean W.H.I.	1997	KRT17
46	Keratin 16 and keratin 17 mutations cause pachyonychia congenita. (7539673)	McLean W.H.I.... Munro C.S.	1995	KRT17, KRT16
47	Mutation of a type II keratin gene (K6a) in pachyonychia congenita. (7545493)	Bowden P.E.... Turner R.J.	1995	KRT17, KRT16, KRT6A
48	A gene for pachyonychia congenita is closely linked to the keratin gene cluster on 17q12-q21. (7529318)	Munro C.S.... Strachan T.	1994	KRT17

Genes related to pachyonychia congenita according to GeneCards:

(show all 16)

id	Symbol	Description	Score	GeneCards Section Context
1	KRT6B	keratin 6B	11.1	Summaries, Publications
2	KRT17	keratin 17	11.1	Publications, Summaries
3	KRT16	keratin 16	11.1	Summaries, Publications
4	KRT6A	keratin 6A	11.1	Summaries, Publications
5	KRTAP17-1	keratin associated protein 17-1	11.0	Publications
6	KRT5	keratin 5	11.0	Publications
7	KRTAP11-1	keratin associated protein 11-1	11.0
8	KRT81	keratin 81	11.0
9	KRT86	keratin 86	11.0
10	KRT2	keratin 2	11.0
11	KRT72	keratin 72	11.0
12	KRT9	keratin 9	11.0
13	KRT6C	keratin 6C	11.0
14	GJB6	gap junction protein, beta 6, 30kDa	11.0	Publications
15	FLG	filaggrin	11.0	Publications
16	PCSK5	proprotein convertase subtilisin/kexin type 5	11.0

Pathways related to pachyonychia congenita according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Cytoskeletal Signaling3	9.0	KRT5, KRT6A, KRT17, KRT6B, KRT6C
2	Cytoskeleton remodeling Keratin filaments10	8.5	KRT5, KRT16, KRT6A, KRT17, KRT6C, KRT2
3	Cytoskeleton remodeling_Keratin filaments41	8.3	KRT2, KRT6C, KRT17, KRT6A, KRT16, KRT5

Compounds related to pachyonychia congenita according to GeneDecks:

id	Compound	Score	Top Affiliating Genes
1	acitretin32 9 9	11.7	KRT5, KRT17
2	dithranol32	9.3	KRT16, FLG
3	calcipotriol32 42 9 9	12.1	FLG, KRT5, KRT16
4	retinoid32	8.6	FLG, KRT5, KRT16, KRT17, KRT2
5	retinoic acid32 42 18	10.5	FLG, KRT5, KRT16, KRT17, KRT2

Cellular components related to pachyonychia congenita according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	intermediate filament	GO:005882	7.1	KRTAP17-1, KRT6C, KRT17, KRT6A, KRT86, KRT16
2	keratin filament	GO:045095	6.7	KRT5, KRTAP11-1, KRT2, KRT9, KRT6C, KRT72

Biological processes related to pachyonychia congenita according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	ectoderm development	GO:007398	9.7	KRT6B, KRT6A
2	cytoskeleton organization	GO:007010	9.4	KRT16, KRT86, KRT6C
3	epidermis development	GO:008544	8.8	KRT5, KRT16, KRT17, KRT9, KRT2

Molecular functions related to pachyonychia congenita according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	structural constituent of cytoskeleton	GO:005200	8.1	KRT5, KRT2, KRT9, KRT6B, KRT17, KRT6A
2	structural molecule activity	GO:005198	7.8	FLG, KRT86, KRT81, KRT72, KRT6C, KRTAP11-1