Having a child with a genetic disorder directly impacts a couple's relationship due to increased care demands. Most research on couple relationships in the context of having a child with a disability has been done in well-resourced, developed countries. In South Africa, the black South African population has been historically disadvantaged resulting in high rates of unemployment and poverty, and disruption of the family system. The purpose of this study was to explore the impact of having a child with a genetic disorder on the couple relationship in a low socio-economic setting. Thirteen black South African mothers of a child with a confirmed or suspected genetic disorder participated in the study. All participants were recruited while waiting to be seen for a follow-up appointment by a medical geneticist at a Genetic Clinic in Johannesburg, South Africa between 2016 and 2019. Data were collected through semi-structured interviews lasting between 25 and 60 min and analyzed using thematic content analysis. Findings showed that mothers of a child with a genetic disorder in this low socio-economic setting frequently felt unsupported and carried the responsibility of childcare alone. The majority of participants wanted more tangible and emotional support from their partners and without this support they felt isolated and alone. The participants used many different coping strategies to deal with the distress of having a child with a genetic disorder but most frequently they described using 'acceptance'. Participants' partners were more often reported to use escape-avoidance strategies such as abandonment, denying paternity, withdrawal, and partner-blame. We suggest that mothers of a child with a genetic disorder should consult with a genetic counselor in addition to a medical geneticist to enable the provision of emotional support.

Genetic counseling has been shown to increase patient empowerment leading to positive outcomes. However, in the Johannesburg state healthcare system, the genetic counseling service is underutilized. Individuals with genetic disorders present with a variety of symptoms and are frequently referred to allied healthcare professionals for management; therefore, these professionals are in a unique position to identify appropriate patients and refer them for genetic counseling. This study aimed to determine whether allied health professionals, including physiotherapists, occupational therapists, and speech and language therapists, were aware of genetic counseling services in Johannesburg, South Africa, and whether they had previously referred patients to these services. The study also aimed to identify barriers and facilitators to referral. An adapted paper-copy questionnaire was administered to allied health professionals working at one of three state hospitals in Johannesburg. A total of 57 participants were included in this study. Results indicated that 29/57 (50.9%) of allied health professionals knew that genetic counseling services were available but only 15/29 (51.7%) of those who knew of the service had referred patients to these services in the last year. Barriers to referral included misconceptions about the role of genetic counselors, insufficient knowledge of which patients would benefit from genetic counseling, and being unable to obtain appropriate information from the Genetics Clinic for patient referral. However, allied health professionals recognized the benefit of genetic counseling and 53/57 (93%) wanted to increase their genetics knowledge. Therefore, genetics education of allied health professionals, and improved information regarding the referral procedure for genetic counseling, may improve the number of patients referred.

BACKGROUNDParenting a child who has an intellectual disability has been shown to increase the risk for developing depression. The purpose of this study was to screen for depression and to determine if there is an association between depressive symptoms and certain sociodemographic factors in mothers with a child diagnosed with Down syndrome in state health care facilities in Johannesburg.METHODSThe study included 30 biological mothers of children between 6 months and 3 years diagnosed with Down syndrome postnatally. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess depression in participants. A 10-item sociodemographic questionnaire was concurrently administered. Data analysis was conducted using descriptive and inferential statistical analysis.RESULTSThe 30 mothers had a mean EPDS score of 9.1 (SD = 5.89) with scores ranging between 0 and 26. Eight mothers (26.7%) screened positive for depression with an EPDS score of 13 or greater. A statistically significant association was found between an HIV-positive status and mothers who had an EPDS score of 13 or greater (P = 0.01). No significant association between depression and various other sociodemographic factors was identified.CONCLUSIONSMothers with a child diagnosed with Down syndrome may be vulnerable to developing depression. A significant association was found between a positive HIV status and symptoms of depression, in mothers with a child diagnosed with Down syndrome. This study indicates the need for further investigations assessing the causes and risk factors resulting in postnatal depression in mothers with a child diagnosed with Down syndrome.

Background. Fanconi anaemia (FA) is a rare genetic disorder of impaired DNA repair that results in physical and haematological consequences in affected individuals. In South Africa (SA), individuals with Afrikaner ancestry are at an increased risk of inheriting disease-causing FA mutations, owing to the three common FANCA (FA, complementation group A) founder mutations present in this population subgroup. Objectives. To describe the physical phenotype of SA patients with FANCA mutations for the purpose of recommending appropriate care for affected individuals. Methods. A structured clinical examination and file-based review were used to evaluate the physical phenotype of 7 patients with compound heterozygous and homozygous FANCA founder mutations, and 1 patient with confirmed FANCA complementation analysis. Descriptive statistical analysis was used to determine the frequency of physical anomalies in Afrikaner patients and to compare the described phenotype to other FA cohorts, including a previously clinically characterised black SA FA cohort. Results. An earlier age of diagnosis of FA in Afrikaner patients, a high frequency of somatic anomalies and a higher-than-expected incidence of the VACTERL/H phenotype were noted. Conclusions. Based on our findings, recommendations for the care of FA patients with Afrikaner ancestry are made, including renal ultrasound evaluation at diagnosis and hearing screening.

Background. Germline pathogenic mutations in cancer susceptibility genes result in inherited cancer syndromes. In the Afrikaner population of South Africa (SA), three founder mutations in the BRCA genes that lead to hereditary breast and ovarian cancer syndrome (HBOCS) have been identified. Objectives. To investigate the uptake and type of molecular testing performed on patients for HBOCS, to determine the prevalence of the three Afrikaner founder BRCA mutations as well as non-founder BRCA mutations in the study population, and to analyse the utility of two mutation prediction models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and Manchester scoring method) in assisting with the decision for the most cost-effective testing option. Methods. A retrospective file review was performed on counsellees of self-reported Afrikaner ancestry from Johannesburg, SA (2001 - 2014), with a personal or family history of breast and/or ovarian cancer. Demographic and family history information was recorded and Manchester and BOADICEA scores were calculated for each patient. Results. Of 86 unrelated counsellees whose files were reviewed, 54 (62.8%) underwent BRCA genetic testing; 18 (33.3%) tested positive for a mutation, and 14 of these (77.8%) for an Afrikaner founder mutation. Twelve counsellees had the BRCA2 c.7934delG mutation. Four non-founder mutations were identified. BOADICEA scores were significantly higher in counsellees who tested positive for a mutation than in those who tested negative. Conclusions. Founder mutation testing should be performed as a first-line option. BOADICEA is very useful in identifying counsellees at high risk for a BRCA mutation and also assists with the decision to pursue further testing following a negative founder mutation result. These findings assist in guiding an informed genetic counselling service for at-risk individuals with an Afrikaner background.

Fanconi anemia (FA) is a rare disorder of DNA repair, associated with various somatic abnormalities but characterized by hematological disease that manifests as bone marrow aplasia and malignancy. The mainstay of treatment, in developed nations, is hematopoietic stem cell transplantation (HSCT) with subsequent surveillance for solid organ and non-hematological malignancies. In South Africa, FA in the Black population is caused by a homozygous deletion mutation in the FANCG gene in more than 80% of cases. Many affected patients are not diagnosed until late in the disease course when severe cytopenia and bone marrow aplasia are already present. Most patients are not eligible for HSCT at this late stage of the disease, even when it is available in the state health care system. In this study, the hematological presentation and disease progression in 30 Black South African patients with FA, confirmed to have the FANCG founder mutation, were evaluated and compared to those described in other FA cohorts. Our results showed that patients, homozygous for the FANCG founder mutation, present with severe cytopenia but progress to bone marrow failure at similar ages to other individuals affected with FA of heterogeneous genotype. Further, the incidence of myelodysplastic syndrome is similar to that which has been previously described in other FA cohorts. Although severe cytopenia at presentation may be predicted by a higher number of somatic anomalies, the recognition of the physical FA phenotype in Black South African patients is challenging and may not be useful in expediting referral of suspected FA patients for tertiary level investigations and care. Given the late but severe hematological presentation of FA in Black South African patients, an investigative strategy is needed for earlier recognition of affected individuals to allow for possible HSCT and management of bone marrow disease.

Purpose: Fanconi anemia is a genotypically and phenotypically heterogeneous condition, characterized microscopically by chromosomal instability and breakage. Affected individuals manifest growth restriction and congenital physical abnormalities; most progress to hematological disease including bone marrow aplasia. Black South African Fanconi anemia patients share a common causative founder mutation in the Fanconi G gene in 80% of cases (637_643delTACCGCC). The aim of this study was to investigate the genotype–physical phenotype correlation in a cohort of individuals homozygous for this mutation. Methods: Thirty-five black patients were recruited from tertiary level hematology/oncology clinics in South Africa. Participants were subjected to a comprehensive clinical examination, documenting growth, congenital anomalies, and phenotypic variability. Results: Descriptive statistical analysis showed significant growth abnormalities in many patients and a high frequency (97%) of skin pigmentary anomalies. Subtle anomalies of the eyes, ears, and hands occurred frequently (≥70%). Apart from malformations of the kidney (in 37%) and gastrointestinal tract (in 8.5%), congenital anomalies of other systems including the cardiovascular and central nervous systems, genitalia, and vertebrae were infrequent (<5%). Conclusion: The diagnosis of Fanconi anemia in black South African patients before the onset of hematological symptoms remains a clinical challenge, with the physical phenotype unlikely to be recognized by those without dysmorphology expertise. Genet Med 16 5, 400–406.

BACKGROUND:Huntington disease (HD) is an autosomal dominant neurodegenerative disorder for which genetic counseling and testing are available in South Africa.OBJECTIVE:The purpose of this study was to assess the utilization of the services available in Johannesburg for diagnostic, predictive, and prenatal genetic testing and counseling for HD and the characteristics of the patients who use them.SUBJECTS AND METHODS:A retrospective study was conducted using records of patients (n=287) who had genetic counseling and/or testing for HD through the Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, between January 1998 and December 2006. Age, gender, number of children, ethnicity, and test results were analyzed.RESULTS:Of the 287 patients included in this study, 77% had diagnostic testing, 20% predictive, and 3% prenatal testing. In the diagnostic group, 47% of subjects tested positive for HD1 and 9% for HDL2 (all Black or of mixed ancestry). Altogether, 66.7% of subjects in the predictive group had testing and 39.5% were positive. In both groups, White subjects were overrepresented. In seven prenatal tests, three fetuses (including a set of twins) tested positive for HD and termination of pregnancy was requested.DISCUSSION AND CONCLUSION:The HD services for predictive and prenatal testing appear to be underutilized, especially by Black individuals, possibly because of lack of awareness among these individuals and among healthcare providers and/or a lower HD prevalence in this group. Recognition of and testing for HDL2 is important in South Africa's large Black population, and HD testing services cannot be considered complete unless testing for both HD1 and HDL2 are undertaken.

Fetal abnormalities are congenital abnormalities identified prenatally. Women who have a fetal abnormality detected often have to make difficult decisions regarding continuation or termination of the pregnancy. The aims of this research project were: to investigate some of the factors that influenced the decision to terminate a pregnancy in which fetal abnormalities were diagnosed; and to determine the implications for genetic counseling practice in South Africa. The study was retrospective and file-based. A total of 171 women counseled for fetal abnormalities, between 2002 and 2006, were identified and relevant data were collected from their records. Altogether 116/170 (68.2%) women were offered termination of pregnancy, and 73/113 (65%) requested the procedure. Early gestation, gestation at the time termination was offered, and ethnicity of the patient, were significantly associated with a termination request. Black patients were less likely to request termination, but more likely to receive a late diagnosis than other patients. Genetic counselors need to adopt an advocacy and educational role to improve this situation. Furthermore, a better understanding of the cultural and ethnicity-related issues is required.

Combined deficiency of factor V and factor VIII (F5F8D) is caused by mutations in one of 2 genes, either LMAN1 or MCFD2. Here we report the identification of mutations for 11 additional F5F8D families, including 4 novel mutations, 2 in MCFD2 and 2 in LMAN1. We show that a novel MCFD2 missense mutation identified here (D81Y) and 2 previously reported mutations (D89A and D122V) abolish MCFD2 binding to LMAN1. Measurement of platelet factor V (FV) levels in 7 F5F8D patients (4 with LMAN1 and 3 with MCFD2 mutations) demonstrated similar reductions to those observed for plasma FV. Combining the current data together with all previous published reports, we performed a genotype-phenotype analysis comparing patients with MCFD2 mutations with those with LMAN1 mutations. A previously unappreciated difference is observed between these 2 classes of patients in the distribution of plasma levels for FV and factor VIII (FVIII). Although there is considerable overlap, the mean levels of plasma FV and FVIII in patients with MCFD2 mutations are significantly lower than the corresponding levels in patients with LMAN1 mutations. No differences in distribution of factor levels are observed by sex. These data suggest that MCFD2 may play a primary role in the export of FV and FVIII from the ER, with the impact of LMAN1 mediated indirectly through its interaction with MCFD2.

Oculocutaneous albinism (OCA) is an inherited disorder resulting in hypopigmentation of the skin, hair, and eyes. OCA type 2 (tyrosinase-positive) is the most common recessively inherited disorder among southern African Blacks. OCA2 is also seen in southern African Caucasoids, but is less frequent. The gene responsible for this type of albinism, P, is the human homolog of the mouse pink-eyed dilution gene. Mutations at this locus are also responsible for the milder hypopigmentation phenotype seen in individuals with brown oculocutaneous albinism (BOCA). A common African P mutation was identified in Black OCA2 individuals, and has since been shown to occur in Black individuals with brown OCA as well. This mutation is a 2.7 kb interstitial deletion. In this study, we undertook to screen the coding region of the P gene for mutations in the non-2.7 kb deletion alleles of OCA2 patients who did not carry the deletion allele in either one or both of their P genes. We identified four mutations (A334V, 614delA, 683insT, 727insG) in a group of 39 unrelated Black OCA2 patients with a total of 52 non-2.7 kb deletion OCA2 genes. When taking all OCA2 cases into consideration, including those homozygous for the 2.7 kb deletion mutation, these account for a further 1.7% of OCA2 mutations in southern African Blacks, increasing the overall mutation detection rate to 78.7%. Three mutations (E678K, L688F, I370T) were identified in a group of 15 Black patients with an initially unclassified type of OCA and another three mutations (IVS 14-2 (a→g), V350M, P743L) were identified in nine Caucasoid OCA patients. Relatively few mutations, all with low frequency, were identified in the non-2.7 kb deletion OCA genes. We propose that other mutations may lie either within intronic sequence or within the promoter region of the gene. Hum Mutat 15:166–172, 2000. © 2000 Wiley-Liss, Inc.