THE GENETIC DISORDERS AMONG SEPHARDIC JEWS by Caleen Blackman Masters of Science in Genetic Counseling May, 2002

The Jewish community is very diverse, encompassing many different ethnic groups. The two largest groups in the modern Jewish population are the Ashkenazi and Sephardic Jews. The Ashkenazi Jews claim ancestry from Eastern European countries such as Germany, Poland, and Russia. The Sephardic Jews claim ancestry from Mediterranean countries such as Spain, Portugal, and Morocco. Each of these two groups have a distinct culture and language, but the extent of their genetic differences is not well known. Currently, there is a great deal of more information available to genetic counselors on the genetic diseases commonly seen in the Ashkenazi Jews, than those seen in the Sephardic population. The purpose of this thesis is to determine what data are available on the incidence of genetic diseases occurring within the Sephardic Jewish population, relative to the incidence in the general population. It was hoped that this data might yield support for the development of much needed guidelines for genetic counselors on genetic carrier testing in Sephardic Jews. The information on the genetic diseases in the Sephardic population was obtained through an extensive literature search for journal articles using PubMed (www.ncbi.nlm.gov/PubMed/). A bibliography was constructed from the articles collected and reference lists from these articles were reviewed in order to identify additional resources. Twenty-seven disorders were identified as occurring within one or a few of fourteen different Sephardic sub-ethnic groups and not in the Sephardic population as a whole. This research identified which genetic disorders occur, or occur at a high frequency in some Sephardic ethnic groups for which genetic counselors can offer genetic carrier testing if appropriate and available. It is hoped that this information will be help provide a valuable preliminary groundwork for guidelines of genetic testing offered to individuals of Sephardic Jewish ethnicity who seek genetic counseling.

MUTATION ANALYSIS OF THE MTM1 GENE IN POTENTIAL FEMALE CARRIERS OF X-LINKED MYOTUBULAR MYOPATHY by Linda Hasadsri Masters of Science in Genetic Counseling May, 2001

X-linked recessive myotubular myopathy (XLMTM) is a rare, congenital disorder characterized by severe muscle weakness at birth. Spontaneous movements are typically absent or weak, and affected males often die within the first year of life from respiratory failure or distress. The majority of cases are caused by mutations in a gene known as MTM1, located near the tip of the distal arm of the human X chromosome (Xq28). In X-linked recessive conditions, the risk of an affected male to be a sporadic case bearing a new mutation is generally thought to be one-third. This implies that the risk of a mother of an affected male to be a carrier is two-thirds. The purpose of this study is to detect the presence of mutations in the coding region of MTM1 among three unrelated women who might possibly be carriers. Two of these women have had affected sons, while the third is affected with an unknown myopathy and has a muscle biopsy suggestive of heterozygosity for XLMTM. Based on the fact that women who have had an affected son are at a two-thirds risk of being a carrier, I believe that the two subjects who have had offspring with XLMTM have a significant chance of carrying a mutation in MTM1. To test this hypothesis, it was necessary to sequence the exons and intron-exon boundaries of the MTM1 gene in this group of women. No mutations in the coding region and neighboring splice sites of MTM1 were found in two of the women. However, in one participant, a single base pair substitution of unknown significance was discovered in exon 4. Because this variant was not reported in the existing literature and the subject's affected son was unavailable for testing, it cannot be determined at this time whether this alteration is associated with the disease phenotype. I recommend that further studies be conducted to fully ascertain whether or not it is indeed a deleterious mutation in order to provide a more accurate assessment of the subjectís carrier status and subsequent recurrence risk.

GENETIC COUNSELING & PRENATAL CARE: A STUDY OF WOMEN WHO USE DONOR INSEMINATION TO BECOME PREGNANT by Emily Sharon Parkhurst Masters of Science in Genetic Counseling May, 2001

As growing numbers of lesbian women choose donor insemination (DI) to become pregnant, little is known about the prenatal care and genetic counseling experiences of these women. Although donor insemination was once an exclusive procedure for infertile couples, DI has become more widely available, especially to lesbians and single women. Negative assumptions about the parental fitness of homosexuals and the cultural and personal barriers to health care that lesbians encounter, lead me to hypothesize that although lesbians may be less satisfied with the prenatal care and genetic counseling they receive than heterosexual women. By trying to understand both the attitudes and experiences women who use DI to become pregnant, the study would help educate health care providers about how to better serve these women, especially lesbians. A 49 item questionnaire was designed based on a pre-tested and validated instrument, and additional self-constructed questions. These questions assessed demographics as well as previous knowledge and satisfaction with prenatal care and genetic counseling. Fliers were distributed to two infertility clinics and several support groups; announcements were also posted on several internet message boards and support groups. Participants could complete the survey electronically on the internet or by mail. 56 surveys were completed with the vast majority of subjects were well educated and from high socio-economic status. Most participants were very satisfied with the prenatal care and genetic counseling they received. Previous knowledge correlated with education, but did not affect satisfaction. Lesbians and single women were more likely to see a genetic counselor and opt for amniocentesis than wives of infertile men. Lesbians were also more likely to visit a nurse-midwife than a traditional outpatient clinic. Lesbians were more satisfied with their prenatal care and genetic counseling compared to similar heterosexual women, going against my hypothesis. Lesbians may be more careful and picky in choosing a prenatal care provider that will be more supportive. Another reason for higher satisfaction in lesbians may be that lesbians expect discriminatory attitudes from their prenatal care provider and when they find their practitioner sensitive and understanding, they are relieved. Participants were able to elaborate on their genetic counseling experiences. Those who expressed dissatisfaction with their genetic counseling felt frustrated and unsupported when they received bad news. Based on these results, genetic counselors should strive to more adequately support those patients in difficult situations. As there was no evidence of prejudice or homophobia, counselors should continue their cultural competency and sensitivity to lesbians who use donor insemination.

FETAL ECHOGENIC BOWEL: A RETROSPECTIVE STUDY by Cori DeLinn Roper Masters of Science in Genetic Counseling May, 2001

Fetal echogenic bowel is a specific ultrasound marker seen during the second trimester of pregnancy that has been associated with pathological conditions such as aneuploidy, cystic fibrosis, transplacental infections, placental dysfunction, and intrauterine growth retardation. This is a retrospective study of 147 patients referred for genetic counseling because of fetal echogenic bowel between August 12, 1991 and December 29, 2000. These patients were unselected members of a large health plan that offers routine second trimester sonographic anatomical surveys. In addition to genetic counseling, patients were offered testing to rule out the aforementioned conditions and were referred to a high-risk obstetrical clinic. Of the 147 patients reviewed in this study, 144 accepted genetic counseling. Information regarding genetic counseling or pregnancy outcome was unavailable on four patients. The remaining 140 patients were seen by genetic counselors at the southern California Kaiser Permanente Woodland Hills or Panorama City Genetics offices. Summaries from the counseling session and test results were available for review in the genetics files of all 140 patients. Pregnancy outcome and follow-up was available through clinic chart reviews on 109 patients. The purpose of this study is to 1) compare the prevalence of aneuploidy, cystic fibrosis, and transplacental infection in fetuses with echogenic bowel from an unselected, multi-ethnic population to that stated in the literature; 2) determine if fetal echogenic bowel is a significant indicator for poor pregnancy outcome and warrants prenatal testing and close follow-up in a high-risk obstetrical clinic. The goal of this study is to provide information regarding the relevance of this ultrasound finding in an unselected population routinely screened for anatomical abnormalities including markers for aneuploidy. This information is useful in determining the impact that screening has on genetic counseling, prenatal testing, and pregnancy management.

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