Challenges to effective and autonomous genetic testing and counseling for ethno-cultural minorities: a qualitative study.

BACKGROUND: The Arab population in Israel is a minority ethnic group with its own distinct cultural subgroups. Minority populations are known to underutilize genetic tests and counseling services, thereby undermining the effectiveness of these services among such populations. However, the general and culture-specific reasons for this underutilization are not well defined. Moreover, Arab populations and their key cultural-religious subsets (Muslims, Christians, and Druze) do not reside exclusively in Israel, but are rather found as a minority group in many European and North American countries. Therefore, focusing on the Arab population in Israel allows for the examination of attitudes regarding genetic testing and counseling among this globally important ethnic minority population. METHODS: We used a qualitative research method, employing individual interviews with 18 women of childbearing age from three religious subgroups (i.e., Druze, Muslim, and Christian) who reside in the Acre district, along with focus group discussions with healthcare providers (HCPs; 9 nurses and 7 genetic counselors) working in the same geographical district. RESULTS: A general lack of knowledge regarding the goals and practice of genetic counseling resulting in negative preconceptions of genetic testing was identified amongst all counselees. Counselors' objective of respecting patient autonomy in decision-making, together with counselees' misunderstanding of genetic risk data, caused uncertainty, frustration, and distrust. In addition, certain interesting variations were found between the different religious subgroups regarding their attitudes to genetic counseling. CONCLUSIONS: The study highlights the miscommunications between HCPs, particularly counselors from the majority ethno-cultural group, and counselees from a minority ethno-cultural group. The need for nuanced understanding of the complex perspectives of minority ethno-cultural groups is also emphasized. Such an understanding may enhance the effectiveness of genetic testing and counseling among the Arab minority group while also genuinely empowering the personal autonomy of counselees from this minority group in Israel and other countries.

COG6-CDG: Expanding the phenotype with emphasis on glycosylation defects involved in the causation of male disorders of sex development.

COG6-congenital disorder of glycosylation (COG6-CDG) is caused by biallelic mutations in COG6. To-date, 12 variants causing COG6-CDG in less than 20 patients have been reported. Using whole exome sequencing we identified two siblings with a novel homozygous deletion of 26 bp in COG6, creating a splicing variant (c.518_540 + 3del) and a shift in the reading frame. The phenotype of COG6-CDG includes growth and developmental retardation, microcephaly, liver and gastrointestinal disease, hypohydrosis and recurrent infections. We report two patients with novel phenotypic features including bowel malrotation and ambiguous genitalia, directing attention to the role of glycoprotein metabolism in the causation of disorders of sex development (DSD). Searching the glycomic literature, we identified 14 CDGs including males with DSD, a feature not previously accentuated. This study broadens the genetic and phenotypic spectrum of COG6-CDG and calls for increasing awareness to the central role of glycosylation processes in development of human sex and genitalia.

Genetic counseling of high-risk isolated populations: A worldwide challenge.

BACKGROUND: Isolated populations with high rates of consanguinity and genetic disorders can be found in most parts of the world. The aim of our paper was to highlight the unique challenges faced in genetic counseling for such patients and to discuss the ways to facilitate the difficulties, with an emphasis on the crucial role of electronic medical records (EMR). CASE: We report a couple presenting with elevated maternal alpha-fetoprotein in three pregnancies, in which an erroneous diagnosis of epidermolysis bullosa was established in the past and carried along through several years. The live born proband had no evidence of skin disease; however, soon after birth she was diagnosed with congenital nephrotic syndrome. Sequencing of NPHS1 gene yielded a homozygous likely pathogenic genetic variant c.2104G > A (p.Gly702Arg). Population screening performed in the village of residence revealed a carrier frequency of 1-47. This high frequency justified including testing for the founder genetic variant in the national program for population screening. CONCLUSIONS: Our report highlights the caution, suspicion and time investment which should be practiced and addressed in genetic counseling of high-risk isolated populations. Using EMR may facilitate reaching the correct diagnosis, enable accurate genetic counseling and provide information for decision-making to the couples, as well as "save" a large community from devastating diseases.