title: [Mutation analysis for a Chinese family featuring X-linked alpha thalassemia/mental retardation syndrome].
abstract: OBJECTIVE
  To identify potential mutation in a Chinese family featuring X-linked alpha thalassemia/mental retardation syndrome (ATR-X).
  
  
  METHODS
  Based on clinical symptoms and inheritance pattern, linkage analysis of X chromosome short tandem repeats (X-STR) loci was carried out to locate the candidate gene. Subsequently, sequences of exons and exon-intron boundaries of the candidate gene were amplified with polymerase chain reaction (PCR). Potential mutations were detected by direct DNA sequencing. All patients were also analyzed for the trait of thalassemia.
  
  
  RESULTS
  Linkage analysis indicated the candidate gene to be ATRX. Subsequently, a homozygous missense mutation c.736C>T (p.R246C) was found in exon 9 of ATRX in all of the 3 patients. And a heterozygous mutation c.736C>T (p.R246C) was also identified in the patient's mother and grandmother. Similar mutations were not detected in other members of the family. Alpha thalassemia was detected in the proband and another patient, whose genotypes were determined as -α(3.7)/αα and --(sea)/αα, respectively.
  
  
  CONCLUSIONS
  Missense mutation of c.736C>T in ATRX gene is a mutation hotspot, and p.R246C may disturb the function of ATRX-DNMT3-DNMT3L domain (ADD), which may be responsible for the disease in this family.
authors: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University,Guangzhou, Guangdong 510080, P.R. China. zhengchen19@hotmail.com.
authors: Shao-bin
authors: SB
authors: Lin
authors: Hong-yu
authors: HY
authors: Sun
authors: Xin-ming
authors: XM
authors: Song
authors: Lu-ming
authors: LM
authors: Chen
authors: Min-lian
authors: ML
authors: Du
authors: Zheng
authors: Z
authors: Chen
mesh_terms: D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D000075924:X-linked Nuclear Protein; D017085:alpha-Thalassemia / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein