Molecular characterization of a novel x-linked syndrome involving developmental delay and deafness

作者：Hildebrand Michael S^*; de Silva Michelle G; Tan Tiong Yang; Rose Elizabeth; Nishimura Carla; Tolmachova Tanya; Hulett Joanne M; White Susan M; Silver Jeremy; Bahlo Melanie; Smith Richard J H; Dahl Hans Henrik M

来源：American Journal of Medical Genetics, Part A, 2007, 143A(21): 2564-2575.

DOI：10.1002/ajmg.a.31995

• x-linked syndrome
• developmental delay
• sensorineural hearing loss
• POU3F4 deletion
• CHM gene

X-linked syndromes associated with developmental delay and sensorineural hearing loss (SNHL) have been characterized at the molecular level, including Mohr-Tranebjaerg syndrome and Norrie disease. In this study we report on a novel X-linked recessive, congenital syndrome in a family with developmental delay and SNHL that maps to a locus associated with mental retardation (MR) for which no causative gene has been identified. The X-linked recessive inheritance and congenital nature of the syndrome was confirmed by detailed clinical investigation and the family history. Linkage mapping of the X-chromosome was conducted to ascertain the disease locus and candidate genes were screened by direct sequencing and STRP analysis. The recessive syndrome was mapped to Xp11.3-q21.32 and a deletion was identified in a regulatory region upstream of the POU3F4 gene in affected family members. Since mutations in POU3F4 cause deafness at the DFN3 locus, the deletion is the likely cause of the SNHL in this family. The choroideremia (CHM) gene was also screened and a novel missense change was identified. The alteration changes the serine residue at position 89 in the Rab escort 1 protein (REP-1) to a cysteine (S89C). Prenylation of Rab proteins was investigated in patients and the location of REP-1 expression in the brain determined. However, subsequent analysis revealed that this change in CHM was polymorphic having no effect on REP-1 function. Although the causative gene at the MR locus in this family has not been identified, there are a number of genes involved in syndromic and nonsyndromic forms of MR that are potential candidates.

• 出版日期2007-11-1
• 单位河北医科大学