Overview on the first human cytogenetic research in Sudan

Introduction: The present study is the first human cytogenetic project in Sudan which was titled: Cytogenetic and FISH analyses in Sudanese patients with dysmorphic features, ambiguous genitalia, and infertility. The aim of the present study was not only to characterize the genetic alterations in patients with dysmorphic features, ambiguous genitalia and/or infertility among Sudanese population, but also to attract the medical community attention to the importance of human cytogenetics in clinical genetics practice, and also to facilitate the introduction and clinical application of such valuable service in Sudan. Materials and Methods: In this study chromosomal G–banding and fluorescence in situ hybridisation (FISH) analysis were performed on 44 Sudanese patients, 29 females, 14 males, and one patient with unassigned sex. Patients age ranging between 17 days-39 years (mean 18 years), Of the 44 patients, 20 had ambiguous genitalia, 8 dysmorphic features, 11 have puberty and/or fertility complains, and 5 were healthy individual (parents of 3 patients with dysmorphic features). Results: Cytogenetic analysis of 20 patients complaining of ambiguous genitalia (13 females and 6 males, and one case with unassigned sex) showed that 8 has karyotypes different from their assigned sex and the other cases showed karyotypes consistent with Edward syndrome (47,XX,+18) (case 7), and a case with 45,Xdel(X)(p11) (case 11) respectively, when using FISH the 45,Xdel(X)(p11) case showed translocation of the SRY (sex-determining region Y), gene to the active X chromosome. For the 8 patients of dysmorphic features; five showed karyotypes consistent with Down syndrome, of which one showed Robertsonian translocation, with both FISH and ordinary G-banding, and the other three showed normal karyotypes. All the parents showed normal karyotypes. Among the infertility cases all showed normal karyotypes, except for two which showed karyotypes consistent with Turner syndrome and one which showed a male karyotype although the case was raised as a female; ultrasound showed a mass in the position of prostate. Discussion: The study, the ever first one in Sudan, assured the importance, the possibility, and the need for cytogenetic and FISH analysis in diagnosis, management and genetic counseling of genetic diseases caused by constitutional chromosomal changes among Sudanese patients. Sudan Journal of Medical Sciences Vol. 1(1) 2006: 25-3

Expression of cyclin D1 in oral squamous cell carcinoma

Background: Cyclin D1 expression regulates normal cell cycle. Its deregulation or overexpression may cause disruption in the normal cell cycle control and lead to cancer progression. In this study, we aimed to study the expression of cyclin D1 in oral squamous cell carcinoma (OSCC) and find its association with the different grades of oral tumors, if any.Methods: This cross-sectional study included 40 formalin-fixed paraffin-embedded tissue blocks specimens of OSCC with variable grades. The expression of cyclin D1 was evaluated through immunohistochemical (IHC) staining.Results: A total of 40 (9 female and 31 male) samples were included, with a maleto-female ratio of 3.4:1. The age ranged between 25 and 90 years with an average age of 65.5 years. Twenty-five (62.5%) samples were diagnosed as well-differentiated squamous cell carcinoma (WDSCC) and fifteen (37.5%) as poorly differentiated squamous cell carcinoma (PDSCC). No cases of moderately differentiated squamous carcinoma were included in the study. The expression of cyclin D1 was detected in the cases of WDSCC and a lesser expression was seen in the PDSCC with a P-value of 0.0003, OR 1581 and 95% CI (29.8239 to 83810.7113).Conclusion: Cyclin D1 is expressed in OSCC and stronger expression was detected in WDSCC

A case of Cornelia de Lange syndrome from Sudan

BACKGROUND: Brachmann de Lange syndrome (BDLS) is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. CASE PRESENTATION: Here we present for the first time a case of BDLS from Sudan, a 7-month-old female infant, who was referred as a case of malnutrition. The patient was from a Sudanese western tribe. Clinical investigation showed that the child was a classical case of BDLS, but with some additional clinical findings not previously reported including crowded ribs and tied tongue. CONCLUSION: Reporting BDLS cases of different ethnic backgrounds could add nuances to the phenotypic description of the syndrome and be helpful in diagnosis

Novel associations in disorders of sex development: findings from the I-DSD registry

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.<p></p> Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry.<p></p> Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.<p></p> Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.<p></p> Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.<p></p&gt

Novel associations in disorders of sex development: findings from the I-DSD registry

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.<p></p> Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry.<p></p> Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.<p></p> Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.<p></p> Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.<p></p&gt

Expression of Cyclin D1 in Oral Squamous Cell Carcinoma

Background: Cyclin D1 expression regulates normal cell cycle. Its deregulation or overexpression may cause disruption in the normal cell cycle control and lead to cancer progression. In this study, we aimed to study the expression of cyclin D1 in oral squamous cell carcinoma (OSCC) and find its association with the different grades of oral tumors, if any.  Methods: This cross-sectional study included 40 formalin-fixed paraffin-embedded tissue blocks specimens of OSCC with variable grades. The expression of cyclin D1 was evaluated through immunohistochemical (IHC) staining. Results: There were 9 female and 31 male samples, with a male-to-female ratio of 3.4:1. The age ranged between 25 and 90 years with an average age of 65.5 years. Twenty-five (62.5%) samples were diagnosed as well-differentiated squamous cell carcinoma (WDSCC) and fifteen (37.5%) as poorly differentiated squamous cell carcinoma (PDSCC). No cases of moderately differentiated squamous carcinoma were included in the study. The expression of cyclin D1 was detected in the cases of WDSCC and a lesser expression was seen in the PDSCC with a P-value of 0.0003, OR 1581 and 95% CI (29.8239 to 83810.7113). Conclusion: Cyclin D1 is expressed in  OSCC and stronger expression was detected in WDSCC

46,XY disorder of sex development in a sudanese patient caused by a novel mutation in the HSD17B3 gene

In this study, we present a Sudanese 46,XY patient raised as a female and diagnosed at the age of 20 years with having 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency. She presented with primary amenorrhea, undeveloped breasts and a male pattern of secondary sexual characteristics. Examination of her external genitalia showed type IV genital circumcision. Steroid measurements both in urine and serum pointed to 17β-HSD3 deficiency. A novel homozygous splice-site mutation [c.524 + 2T&gt;A] was detected in intron 7 of the &lt;i&gt;HSD17B3&lt;/i&gt; gene. In this patient, steroid concentration clearly supported both the clinical diagnosis of 17β-HSD3 deficiency and the functional relevance of the mutation. Interestingly, despite of the type IV genital circumcision, the patient expressed her interest in reassigning her sex from female to male.</jats:p

Novel associations in disorders of sex development: findings from the I-DSD Registry.

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases

Changes over time in sex assignment for disorders of sex development

BACKGROUND AND OBJECTIVE: It is unclear whether the proportion of infants with a disorder of sex development who are raised as male or female has changed over time. The temporal trends in sex assignment of affected cases entered in the International Disorder of Sex Development (I-DSD) Registry were studied. METHODS: Cases of disorders of sex development reported as partial androgen insensitivity syndrome (PAIS; n = 118), disorder of gonadal development (DGD; n = 232), and disorder of androgen synthesis (DAS; n = 104) were divided into those who were born before 1990, 1990-1999, and after 1999. External appearance of the genitalia was described by the external masculinization score. RESULTS: The median (5th-95th percentile) external masculinization scores of those infants with PAIS, DGD, and DAS who were raised as boys were 6 (2-9), 6 (3-9), and 6 (1-12), respectively, and were significantly higher than in those raised as girls (2 [0-6], 2 [0-7], and 0 [0-5], respectively); this difference was maintained in the 3 temporal birth cohorts (P < .01). Of the 118 cases in the pre-1990 cohort, 41 (35%) were raised as boys; of the 148 cases in the 1990-1999 cohort, 60 (41%) were raised as boys; and of the 188 cases in the post-1999 cohort, 128 (68%) were raised as boys. CONCLUSIONS: Although there is an association between the external appearance of the genitalia and the choice of sex assignment, there are clear temporal trends in this practice pointing toward an increased likelihood of affected infants being raised as boys. The impact of this change in practice on long-term health outcomes requires additional focus