PMID- 10583221
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20190705
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 107
IP  - 2
DP  - 1999 Nov
TI  - Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia
      (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita
      gene, DKC1.
PG  - 335-9
AB  - Hoyeraal-Hreidarsson (HH) syndrome is a multisystem disorder affecting boys
      characterized by aplastic anaemia (AA), immunodeficiency, microcephaly,
      cerebellar-hypoplasia and growth retardation. Its pathogenesis is unknown.
      X-linked dyskeratosis congenita (DC) is an inherited bone-marrow-failure syndrome
      characterized by skin pigmentation, nail dystrophy and leucoplakia which usually 
      develop towards the end of the first decade of life. AA occurs in >90% of cases
      of DC. We speculated that mutations in the gene responsible for X-linked DC
      (DKC1) may account for the HH syndrome, due to the phenotypic similarities
      between the disease in respect of AA and gender bias. We therefore analysed the
      DKC1 gene in two HH families. In one family a nucleotide change at position 361(A
      --> G) in exon 5 was found in both affected brothers; in the other family a
      nucleotide change at position 146(C --> T) in exon 3 was found in the affected
      boys. The finding of these two novel missense DKC1 mutations demonstrates that HH
      is a severe variant of DC. They also show that mutations in DKC1 can give rise to
      a very wide clinical spectrum of manifestations. Boys with unexplained AA or
      immunodeficiency should be tested for mutations in DKC1 even though they may lack
      diagnostic features of DC.
FAU - Knight, S W
AU  - Knight SW
AD  - Department of Haematology, Imperial College School of Medicine, Hammersmith
      Hospital, London, U.K.
FAU - Heiss, N S
AU  - Heiss NS
FAU - Vulliamy, T J
AU  - Vulliamy TJ
FAU - Aalfs, C M
AU  - Aalfs CM
FAU - McMahon, C
AU  - McMahon C
FAU - Richmond, P
AU  - Richmond P
FAU - Jones, A
AU  - Jones A
FAU - Hennekam, R C
AU  - Hennekam RC
FAU - Poustka, A
AU  - Poustka A
FAU - Mason, P J
AU  - Mason PJ
FAU - Dokal, I
AU  - Dokal I
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DKC1 protein, human)
RN  - 0 (Nuclear Proteins)
SB  - IM
MH  - Amino Acid Substitution/genetics
MH  - Anemia, Aplastic/*genetics
MH  - Cell Cycle Proteins/*genetics
MH  - Cerebellum/*abnormalities
MH  - Female
MH  - Fetal Growth Retardation/genetics
MH  - Humans
MH  - Immune System Diseases/*genetics
MH  - Infant
MH  - Male
MH  - Microcephaly/genetics
MH  - Mutation, Missense/*genetics
MH  - Nuclear Proteins/*genetics
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Syndrome
EDAT- 1999/12/03 00:00
MHDA- 1999/12/03 00:01
CRDT- 1999/12/03 00:00
PHST- 1999/12/03 00:00 [pubmed]
PHST- 1999/12/03 00:01 [medline]
PHST- 1999/12/03 00:00 [entrez]
AID - bjh1690 [pii]
AID - 10.1046/j.1365-2141.1999.01690.x [doi]
PST - ppublish
SO  - Br J Haematol. 1999 Nov;107(2):335-9. doi: 10.1046/j.1365-2141.1999.01690.x.