PMID- 10364522
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20181113
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 1
DP  - 1999 Jul
TI  - Monodactylous limbs and abnormal genitalia are associated with hemizygosity for
      the human 2q31 region that includes the HOXD cluster.
PG  - 104-10
AB  - Vertebrates have four clusters of Hox genes (HoxA, HoxB, HoxC, and HoxD). A
      variety of expression and mutation studies indicate that posterior members of the
      HoxA and HoxD clusters play an important role in vertebrate limb development. In 
      humans, mutations in HOXD13 have been associated with type II syndactyly or
      synpolydactyly, and, in HOXA13, with hand-foot-genital syndrome. We have
      investigated two unrelated children with a previously unreported pattern of
      severe developmental defects on the anterior-posterior (a-p) limb axis and in the
      genitalia, consisting of a single bone in the zeugopod, either monodactyly or
      oligodactyly in the autopod of all four limbs, and penoscrotal hypoplasia. Both
      children are heterozygous for a deletion that eliminates at least eight
      (HOXD3-HOXD13) of the nine genes in the HOXD cluster. We propose that the
      patients' phenotypes are due in part to haploinsufficiency for HOXD-cluster
      genes. This hypothesis is supported by the expression patterns of these genes in 
      early vertebrate embryos. However, the involvement of additional genes in the
      region could explain the discordance, in severity, between these human phenotypes
      and the milder, non-polarized phenotypes present in mice hemizygous for HoxD
      cluster genes. These cases represent the first reported examples of deficiencies 
      for an entire Hox cluster in vertebrates and suggest that the diploid dose of
      human HOXD genes is crucial for normal growth and patterning of the limbs along
      the anterior-posterior axis.
FAU - Del Campo, M
AU  - Del Campo M
AD  - Division of Dysmorphology, Department of Pediatrics, University of California,
      San Diego, La Jolla, CA, USA.
FAU - Jones, M C
AU  - Jones MC
FAU - Veraksa, A N
AU  - Veraksa AN
FAU - Curry, C J
AU  - Curry CJ
FAU - Jones, K L
AU  - Jones KL
FAU - Mascarello, J T
AU  - Mascarello JT
FAU - Ali-Kahn-Catts, Z
AU  - Ali-Kahn-Catts Z
FAU - Drumheller, T
AU  - Drumheller T
FAU - McGinnis, W
AU  - McGinnis W
LA  - eng
SI  - GDB/D2S1238
SI  - GDB/D2S1244
SI  - GDB/D2S1395
SI  - GDB/D2S1776
SI  - GDB/D2S425
SI  - GDB/D2S426
GR  - HD28315/HD/NICHD NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Genetic Markers)
RN  - 0 (HOXD11 protein, human)
RN  - 0 (HOXD13 protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hoxd3 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 127609-92-1 (HOXA4 protein, human)
SB  - IM
MH  - Child, Preschool
MH  - Chromosomes, Human, Pair 2
MH  - *DNA-Binding Proteins
MH  - Gene Deletion
MH  - Gene Dosage
MH  - Genetic Markers
MH  - Genitalia, Male/abnormalities
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - Infant, Newborn
MH  - Limb Deformities, Congenital/diagnostic imaging/*genetics
MH  - Male
MH  - Molecular Sequence Data
MH  - Multigene Family
MH  - Radiography
MH  - *Transcription Factors
PMC - PMC1378080
EDAT- 1999/06/12 10:00
MHDA- 2000/03/21 09:00
CRDT- 1999/06/12 10:00
PHST- 1999/06/12 10:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/06/12 10:00 [entrez]
AID - S0002-9297(07)63733-1 [pii]
AID - 10.1086/302467 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Jul;65(1):104-10. doi: 10.1086/302467.