PMID- 10504448
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20061115
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 113
IP  - 4
DP  - 1999 Oct
TI  - Identification of novel mutations in basic hair keratins hHb1 and hHb6 in
      monilethrix: implications for protein structure and clinical phenotype.
PG  - 607-12
AB  - Monilethrix is an hereditary hair dystrophy recently shown to be due to mutations
      in the helix termination motif of two type II (basic) human hair keratin genes,
      hHb1 and hHb6. It has been suggested that mutation in hHb1 produces a less severe
      phenotype. We have studied hair keratin genes and clinical features in 18
      unrelated pedigrees of monilethrix from Germany, Scotland, Northern Ireland, and 
      Portugal, in 13 of which mutations have not previously been identified. By
      examining the rod domains of hHb1, hHb3 and hHb6, we have identified mutations in
      nine of the new pedigrees. We again found the glutamine-lysine substitution
      (E413K) in the helix termination motif of hHb6 in two families, and in another,
      the corresponding E413K substitution in the hHb1 gene. In four families a similar
      substitution E402K was present in a nearby residue. In addition two novel
      mutations within the helix initiation motif of hHb6 were found in Scottish and
      Portuguese cases, in whom the same highly conserved asparagine residue N114 was
      mutated to histidine (N114H) or aspartic acid (N114D) residues, respectively. In 
      four other monilethrix pedigrees mutations in these domains of hHb1, hHb3, and
      hHb6 were not found. The mutations identified predict a variety of possible
      structural consequences for the keratin molecule. A comparison of clinical
      features and severity between cases with hHb1 and hHb6 mutations does not suggest
      distinct effects on phenotype, with the possible exception of nail dystrophy,
      commoner with hHb1 defects. Other factors are required to explain the marked
      variation in clinical severity within and between cases.
FAU - Korge, B P
AU  - Korge BP
AD  - Department of Dermatology and Venerology, University of Cologne, Germany.
      Bkorge@mac.genetik.uni-koeln.de
FAU - Hamm, H
AU  - Hamm H
FAU - Jury, C S
AU  - Jury CS
FAU - Traupe, H
AU  - Traupe H
FAU - Irvine, A D
AU  - Irvine AD
FAU - Healy, E
AU  - Healy E
FAU - Birch-MacHin, M
AU  - Birch-MacHin M
FAU - Rees, J L
AU  - Rees JL
FAU - Messenger, A G
AU  - Messenger AG
FAU - Holmes, S C
AU  - Holmes SC
FAU - Parry, D A
AU  - Parry DA
FAU - Munro, C S
AU  - Munro CS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Codon)
RN  - 68238-35-7 (Keratins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Codon
MH  - Female
MH  - Genotype
MH  - Hair Diseases/*genetics
MH  - Humans
MH  - Keratins/chemistry/*genetics
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Phenotype
MH  - Polymorphism, Restriction Fragment Length
MH  - *Protein Structure, Secondary
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
AID - S0022-202X(15)40624-4 [pii]
AID - 10.1046/j.1523-1747.1999.00722.x [doi]
PST - ppublish
SO  - J Invest Dermatol. 1999 Oct;113(4):607-12. doi: 10.1046/j.1523-1747.1999.00722.x.