Breakpoint determination of X;autosome balanced translocations in four patients with premature ovarian failure

Abstract

Premature ovarian failure (POF) is a disorder characterized by amenorrhea and elevated serum gonadotropins before 40 years of age. As X chromosomal abnormalities are often recognized in POF patients, defects of X-linked gene may contribute to POF. Four cases of POF with t(X;autosome) were genetically analyzed. All the translocation breakpoints were determined at the nucleotide level. Interestingly, COL4A6 at Xq22.3 encoding collagen type IV alpha 6 was disrupted by the translocation in one case, but in the remaining three cases, breakpoints did not involve any X-linked genes. According to the breakpoint sequences, two translocations had microhomology of a few nucleotides and the other two showed insertion of 3-8 nucleotides with unknown origin, suggesting that non-homologous end-joining is related to the formation of all the translocations.

Mutational analysis of patients with FGF23-related hypophosphatemic rickets

“…This suggested that transcription of the PHEX gene from a normal allele is suppressed in this patient. It is known that in a balanced X chromosome, autosome translocation, the normal X chromosome is usually inactivated to prevent deleterious monosomy of the translocated autosomal segment (31,32,33). This phenomenon, referred to as skewed X chromosome inactivation, may explain the absence of both the RT-PCR products corresponding to exons 12-22 of the PHEX gene and the wild-type 3 0 RACE product in this patient.…”

Exome sequencing in a family with an X‐linked lethal malformation syndrome: clinical consequences of hemizygous truncating OFD1 mutations in male patients

“…The human androgen receptor (HUMARA) assay was performed as previously reported (9). Genomic DNA of II-2 was digested at 37 • C for 18 h with two methylation-sensitive enzymes, HpaII and HhaI.…”

Study of structural chromosome abnormalities to increase the understanding of human genetic diversity: a commentary on signature of backward replication slippage at the copy number variation junction

“…6,7 Breakpoint junction sequencing has been performed to identify a responsible gene in many patients with apparently balanced chromosomal rearrangements, and the complex repair has sometimes been identified and reported. 8,9 However, in particular, unique UBCAs have not been well analyzed. Thus, the precise mechanism underlying the occurrence of rare structural chromosome rearrangements remains unknown.…”