A founder mutation in the TCIRG1 gene causes osteopetrosis in the Ashkenazi Jewish population

作者：Anderson S L; Jalas C; Fedick A; Reid K F; Carpenter T O; Chirnomas D; Treff N R; Ekstein J; Rubin B Y^*

来源：Clinical Genetics, 2015, 88(1): 74-79.

DOI：10.1111/cge.12448

• Ashkenazi Jewish
• founder mutation
• osteopetrosis
• TCIRG1

Osteopetrosis is a rare and heterogeneous genetic disorder characterized by dense bone mass that is a consequence of defective osteoclast function and/or development. Autosomal recessive osteopetrosis (ARO) is the most severe form and is often fatal within the first years of life; early hematopoietic stem cell transplant (HSCT) remains the only curative treatment for ARO. The majority of the ARO-causing mutations are located in the TCIRG1 gene. We report here the identification and characterization of an A to T transversion in the fourth base of the intron 2 donor splice site (c.117+4AT) in TCIRG1, a mutation not previously seen in the Ashkenazi Jewish (AJ) population. Analysis of a random sample of individuals of AJ descent revealed a carrier frequency of approximately 1 in 350. Genotyping of five loci adjacent to the c.117+4AT-containing TCIRG1 allele revealed that the presence of this mutation in the AJ population is due to a single founder. The identification of this mutation will enable population carrier testing and will facilitate the identification and treatment of individuals homozygous for this mutation.

• 出版日期2015-7
• 单位rutgers