NM_002284.3(KRT86):c.1237G>A (p.Glu413Lys) AND Beaded hair

Clinical significance:Pathogenic (Last evaluated: May 20, 2009)

Review status:1 star out of maximum of 4 stars

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000008048.1

Allele description [Variation Report for ]

Genes:
KRT81:keratin 81, type II [Gene - OMIM]
KRT86:keratin 86, type II [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_002284.3(KRT86):c.1237G>A (p.Glu413Lys)
HGVS:
  • NC_000012.12:g.52306270G>A
  • NG_008086.1:g.9406G>A
  • NM_002284.3:c.1237G>A
  • NP_002275.1:p.Glu413Lys
  • NC_000012.11:g.52700054G>A
Protein change:
E413K; GLU413LYS
Links:
OMIM: 601928.0001; dbSNP: 121909129
NCBI 1000 Genomes Browser:
rs121909129
Molecular consequence:
  • NM_002284.3:c.1237G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Beaded hair (MNLIX)
Synonyms:
Nodose hair; MONILETHRIX (1 patient); Monilethrix
Identifiers:
MedGen: C0546966; Orphanet: 573; OMIM: 158000
Age of onset:
Neonatal/infancy

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Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000028253OMIMPathogenic
(May 20, 2009)
germlineliterature only

PubMed (6)
[See all records that cite these PMIDs]

Korge, B. P., Healy, E., Traupe, H., Punter, C., Mauch, C., Hamm, H., Birch-Machin, M. A., Belgaid, C. E., Stephenson, A. M., Holmes, S. C., Darlington, S., Messenger, A. G., Rees, J. L., Munro, C. S. Monilethrix is caused by mutation in the helix termination peptide of human type II hair keratin hHb6 in three families. (Abstract) J. Invest. Derm. 109: 409-only, 1997.

Summary from all submissions

EthnicityOriginAffectedAlleles observedFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations in the hair cortex keratin hHb6 cause the inherited hair disease monilethrix.

Winter H, Rogers MA, Langbein L, Stevens HP, Leigh IM, Labr├Ęze C, Roul S, Taieb A, Krieg T, Schweizer J.

Nat Genet. 1997 Aug;16(4):372-4.

PubMed [citation]
PMID:
9241275

Characterization and chromosomal localization of human hair-specific keratin genes and comparative expression during the hair growth cycle.

Bowden PE, Hainey SD, Parker G, Jones DO, Zimonjic D, Popescu N, Hodgins MB.

J Invest Dermatol. 1998 Feb;110(2):158-64.

PubMed [citation]
PMID:
9457912
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000028253.1

#EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (6)

Description

Winter et al. (1997) identified a glu413-to-lys (E413K) mutation in affected members in the hair cortical basic keratin 6 in a British monilethrix (158000) family that had been previously been found to show linkage to a type II keratin cluster on 12q13. The mutation in the analogous glutamic acid residue of the type II epidermal keratin 2e has been identified in cases of ichthyosis bullosa of Siemens (600194.0002).

This mutation was originally designated GLU410LYS because the mutation was identified in a partial HB6 cDNA clone; based on the complete HB6 sequence reported by Bowden et al. (1998), Winter et al. (1998) revised the designation of the mutation to glu413 to lys. Glu413 to lys, the most frequently observed mutation in monilethrix, was also found by Korge et al. (1997) in 3 unrelated families.

Korge et al. (1998) sequenced the critical helix termination motif in the 2B domain of the KRTHB6 gene in 13 unrelated families or cases with monilethrix. In 5 of the 13 cases, they found the glu413-to-lys mutation. In 8 cases, however, including 3 in which linkage data were consistent with a defect in the type II keratin locus, no mutation was found in this domain. These findings demonstrate that codon 413 and the glutamic acid, which is residue 117 of the 2B helix, is a mutation hotspot for monilethrix.

Winter et al. (1999) stated that this mutation had been found in 22 cases of monilethrix.

In 15 affected members of 2 unrelated Indian families with monilethrix, Khandpur et al. (2004) identified the E413K mutation in the helix termination motif (HTM) in exon 7 of the KRTHB6 gene; in each family, the mutation segregated with polymorphisms in the HTM motif of the KRTHB1 gene (602153): 1 with 3 novel SNPs in cis and a second with only an intronic SNP. The 9 affected members of family 1 had a localized severe hair defect with beaded appearance confined to the scalp and carried the KRTHB1 polymorphisms in heterozygous state. The 6 affected members of family 2 had a generalized unbeaded hair defect of moderate severity and carried the KRTHB1 polymorphism with 3 SNPs in homozygous state. Presence of both the E413K mutation and variation in the KRTHB1 gene was not observed in 150 randomly selected unaffected controls.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 16, 2015

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