PMID- 12149685
OWN - NLM
STAT- MEDLINE
DCOM- 20020905
LR  - 20190710
IS  - 1531-5037 (Electronic)
IS  - 0022-3468 (Linking)
VI  - 37
IP  - 8
DP  - 2002 Aug
TI  - Clinical features of a form of Hirschsprung's disease caused by a novel genetic 
      abnormality.
PG  - 1117-22
AB  - BACKGROUND/PURPOSE: The aim of this report is to describe the pattern of 
      similarities among the patients, exemplifying a newly recognized form of 
      Hirschsprung's disease (HSCR) caused by mutations of ZFHX1B encoding Smad 
      interacting protein-1. METHODS: Fluorescence in situ hybridization (FISH) using 
      several cDNAs and RP11-BAC clones and mutation gene scanning using direct 
      nucleotide sequencing analysis of polymerase chain reaction (PCR) were conducted. 
      Personal records of the patients also were analyzed retrospectively to confirm 
      the clinical features. RESULTS: All the patients represented isolated cases 
      without any familial tendency. Aganglionic segments were limited to the 
      recto-sigmoid colon in 3 cases and the rectum in one. Chromosomal screening found 
      normal karyotypes in all cases except one, in whom a translocation between 
      chromosomes 2 and 13 was detected. In addition to HSCR, characteristic facial 
      appearance (hypertelorism with strabismus and wide nasal bridge), microcephaly 
      with epilepsy, and severe physical and mental disabilities were found in all the 
      patients. FISH for the patient having the chromosomal abnormality showed that 
      about a 5-Mb cytogenetic deletion flanked at the 2q22 translocation breakpoint. 
      Among 3 genes mapping to this deleted region, 2 nonsense mutations and a 4-base 
      pair deletion were detected in ZFHX1B. CONCLUSIONS: The clinical features of the 
      patients have surprising resemblance and constitute a wide spectrum of 
      neurocristopathies. These findings suggest that the ZFHX1B may be a very 
      important gene for normal embryonic neural crest development. These also indicate 
      that the HSCR can be regarded as a congenital malformation with a background of a 
      multigenetic neurocristopathy. It is of great interest that mutations were 
      located at the same spot (exon 8) of ZFHX1B in 3 of 4 cases, probably accounting 
      for the unique clinical features of this newly recognized form of HSCR.
CI  - Copyright 2002, Elsevier Science (USA). All rights reserved.
FAU - Nagaya, Masahiro
AU  - Nagaya M
AD  - Department of Pediatric Surgery, the Central Hospital, Aichi Prefectural Colony, 
      Kasugai, Japan.
FAU - Kato, Junji
AU  - Kato J
FAU - Niimi, Norihiro
AU  - Niimi N
FAU - Tanaka, Shuiti
AU  - Tanaka S
FAU - Wakamatsu, Nobuaki
AU  - Wakamatsu N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pediatr Surg
JT  - Journal of pediatric surgery
JID - 0052631
RN  - 0 (Codon, Nonsense)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Smad Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (ZEB2 protein, human)
RN  - 0 (Zinc Finger E-box Binding Homeobox 2)
SB  - IM
MH  - Adult
MH  - Child
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 13
MH  - Chromosomes, Human, Pair 2
MH  - *Codon, Nonsense
MH  - DNA-Binding Proteins/metabolism
MH  - Female
MH  - Hirschsprung Disease/*diagnosis/*genetics
MH  - Homeodomain Proteins/*genetics/metabolism
MH  - Humans
MH  - Infant, Newborn
MH  - Male
MH  - Repressor Proteins/*genetics/metabolism
MH  - Retrospective Studies
MH  - *Sequence Deletion
MH  - Smad Proteins
MH  - Trans-Activators/metabolism
MH  - Translocation, Genetic
MH  - Zinc Finger E-box Binding Homeobox 2
EDAT- 2002/08/01 10:00
MHDA- 2002/09/06 10:01
CRDT- 2002/08/01 10:00
PHST- 2002/08/01 10:00 [pubmed]
PHST- 2002/09/06 10:01 [medline]
PHST- 2002/08/01 10:00 [entrez]
AID - S0022346802000362 [pii]
AID - 10.1053/jpsu.2002.34455 [doi]
PST - ppublish
SO  - J Pediatr Surg. 2002 Aug;37(8):1117-22. doi: 10.1053/jpsu.2002.34455.