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G Houck

Publications and source records attributed to G Houck.

5 recordsLinked to original sources
PubMed1999

Accelerated prenatal diagnosis of fragile X syndrome by polymerase chain reaction restriction fragment detection.

Prenatal diagnosis of fragile X syndrome requires detection of the full FMR1 mutation in chorionic villus or amniotic fluid cell samples. Although analysis of genomic DNA restriction fragment pattern is a highly reliable technique for identification of the full FMR1 mutation, standard Southern blot determination of this pattern requires significantly more genomic DNA than is initially available from a prenatal sample. To overcome this limitation we developed a method that determines the diagnostic pattern of genomic restriction fragments from a fraction of a prenatal specimen. The prenatal DNA sample is first digested with EcoRI and EagI, and after agarose gel electrophoresis, the 2- to 10-kb region of the gel is serially sectioned and amplified by polymerase chain reaction. Analysis of prenatal samples from an unaffected male and from a full mutation male showed that this approach generated a diagnostic pattern comparable with a Southern blot of 100-fold more material. This innovation enables laboratories to prenatally diagnose the full FMR1 mutation sooner than standard techniques.

Blotting, Southern↗
PubMed1996

Prenatal diagnosis and carrier screening for fragile X by PCR.

During the past three years, we have conducted fragile X DNA studies for carrier screening and prenatal diagnosis using a previously described PCR protocol that accurately resolves normal FMR1 alleles and premutations and detects most full mutations [Brown et al., JAMA 270:1569-1575, 1996]. A total of 344 pregnant women with a family history of mental retardation of unknown cause were screened and 6 fragile X carriers were identified: two had full mutations, and four had premutations. The mentally retarded relatives of two other women were found to be fragile X positive although the women themselves were not carriers. In all, 6 carriers and 8 fragile X families were identified by this screening. We have also screened 40 pregnant women who were members of previously identified fragile X families, but whose carrier status was unknown. Ten were found to be carriers and were offered prenatal diagnosis. Prospective prenatal testing of 84 carrier women correctly detected 31 fetal samples (19 females, 12 males) with full mutations and 6 with premutations (2 females, 4 males). No false positives but one false negative occurred early on due to undetected maternal cell contamination. In addition, screening of 806 males with developmental delays of unknown cause gave positive results in 33 (4.1%). Potential problems and pitfalls of direct DNA testing are discussed. Because of the proven success of fragile X screening with direct molecular analysis, screening of all undiagnosed individuals with mental retardation and at risk pregnant women should now be considered. The identification of fragile X carriers and prenatal diagnosis of their pregnancies should significantly reduce the prevalence of this syndrome.

Amniocentesis↗
PubMedDate not supplied

Fragile X screening program in New York State.

Most fragile X [fra(X)] males in New York State have not been identified. Hence, a large number of female relatives are unaware of their risks for having an affected child. A program was established in New York State in 1987 to screen for the fra(X) syndrome in mentally retarded males with living relatives. The goal of the program is to identify affected males and inform their families about the diagnosis. In this way relatives would be able to assess their risks for having a fra(X) male. In order to identify the males a screening form was developed to assess 10 features which included physical characteristics, behavior, and family history. Males who exhibited at least 5 of these manifestations were selected for cytogenetic analysis. Any male who had macroorchidism or a family history of mental retardation was also included. A total of 995 males have been screened of which 352 (35%) were selected for cytogenetic analyses. Seventeen (10.5%) of the 161 completed studies were positive for fra(X). A large number of possible female carriers were identified in the families of the propositi. This program identifies fra(X) males in a population of the mentally retarded for whom there had been no previous diagnosis. By using a two-step procedure, it is possible to screen a large population of the mentally retarded for fra(X) without testing each male cytogenetically.

Abnormalities, Multiple↗