Jihad Obeid - Academia.edu (original) (raw)
Papers by Jihad Obeid
Journal of Steroid Biochemistry and Molecular Biology, 1999
The diagnostic term congenital adrenal hyperplasia (CAH) applies to a family of inherited disorde... more The diagnostic term congenital adrenal hyperplasia (CAH) applies to a family of inherited disorders of steroidogenesis caused by an abnormality in one of the five enzymatic steps necessary in the conversion of cholesterol to cortisol. The enzyme defects are translated as autosomal recessive traits, with the enzyme deficient in more than 90% of CAH cases being 21-hydroxylase. In the classical forms of CAH (simple virilizing and salt wasting), owing to 21-hydroxylase deficiency (21-OHD), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Non-classical 21-OHD (NC21OHD) refers to the condition in which partial deficiencies of 21-hydroxylation produce less extreme hyperandrogenemia and milder symptoms. Females do not demonstrate genital ambiguity at birth.The gene for adrenal 21-hydroxylase, CYP21, is located on chromosome 6p in the area of HLA genes. Specific mutations may be correlated with a given degree of enzymatic compromise and the clinical form of 21-OHD. NC21OHD patients are predicted to have mild mutations on both alleles or one severe and one mild mutation of the 21-OH locus (compound heterozygote). In most cases the mutation groups represent one diagnosis (e.g., Del/Del with SW CAH), however we have found several non-correlations of genotype to phenotype. Non-classical and classical patients were found within the same mutation group. Phenotypic variability within each mutation group has important implications for prenatal diagnosis and treatment.Prenatal treatment of 21-OHD with dexamethasone has been utilized for a decade. An algorithm has been developed for prenatal diagnosis and treatment, which, when followed closely, has been safe for both the mother and the fetus, and has been effective in preventing ambiguous genitalia in the affected female newborn. This is an instance of an inborn metabolic error successfully treated prenatally.Since 1986, prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) has been carried out in 403 pregnancies in The New York Hospital–Cornell Medical Center. In 280, diagnoses were made by amniocentesis, while 123 were diagnosed using chorionic villus sampling. Of the 403 pregnancies evaluated, 84 babies were affected with classical 21-OHD. Of these, 52 were females, 36 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 10 weeks of gestation (23 affected female fetuses) was effective in reducing virilization. Thirteen cases had affected female sibs (Prader stages 1–4); 6 of these fetuses were born with entirely normal female genitalia, while 6 were significantly less virilized (Prader stages 1–2) than their sibs, and one was Prader stage 3. Eight newborns had male sibs; 4 were born with normal genitalia, 3 were Prader stages 1–2, and 3 were born Prader stages 3–4. No significant or enduring side effects were noted in either the mothers or the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight, length, or head circumference from untreated, unaffected newborns.Based on our experience, proper prenatal diagnosis and treatment of 21-OHD is effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity of genital surgery, sex misassignment, and gender confusion.
Molecular Genetics and Metabolism, 2008
The Endocrinologist, 2003
... Update: Prenatal Diagnosis for Congenital Adrenal Hyperplasia in 595 Pregnancies. New, Maria ... more ... Update: Prenatal Diagnosis for Congenital Adrenal Hyperplasia in 595 Pregnancies. New, Maria I. MD; Carlson, Ann; Obeid, Jihad; Marshall, Ian; Cabrera, Monina S.; Goseco, Amanda; Lin-Su, Karen; Putnam, Andrea S.; Wei, J. Qing; Wilson, Robert C. ...
The Endocrinologist, 2003
ABSTRACT An abstract is unavailable. This article is available as HTML full text and PDF.
Molecular Genetics and Metabolism, 2007
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) occurs worldwide. T... more Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) occurs worldwide. The most common mutations in the CYP21A2 gene in 716 unrelated patients were analyzed and the mutations were grouped by ethnicity, as defined through self-declaration corroborated by review of pedigrees extending to two or three generations. Prevalent allelic mutations and genotypes were found to vary significantly among ethnic groups, and the predominance of the prevalent mutations and genotypes in several of these populations was significant. There are ethnicspecific mutations in the CYP21A2 gene. A large deletion is prevalent in the Anglo-Saxons; a V281L (1685 G to T) mutation is prevalent in Ashkenazi Jews; an R356W (2109 G to A) mutation is prevalent in the Croatians; an IVS2 AS -13 (A/C to G) mutation is prevalent in the Iranians and Yupik-speaking Eskimos of Western Alaska; and a Q318X (1994 C to T) mutation is prevalent in East Indians. Genotype/phenotype non-correlation was seen when at least one IVS2 AS -13 (A/C to G) mutation in the CYP21A2 gene was present.
![Research paper thumbnail of Erratum to “Ethnic-specific distribution of mutations in 716 patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency” [Mol. Genet. Metabol. 90/4 (2007) 414–421]](https://attachments.academia-assets.com/46946137/thumbnails/1.jpg)
](Molecular Genetics and Metabolism, 2008
The Journal of Clinical Endocrinology & Metabolism, 2004
Dexamethasone (DEX) administration to the pregnant woman has become the treatment of choice for t... more Dexamethasone (DEX) administration to the pregnant woman has become the treatment of choice for the prevention of genital masculinization in female fetuses affected with congenital adrenal hyperplasia (CAH). Although no somatic teratological side effects have been found to date, recent animal research has shown adverse effects of glucocorticoids on brain structures such as the hippocampus, raising concerns about possible functional side effects of DEX on human development. The current survey of 487 children, 1 month to 12 yr of age, focused on cognitive and motor development. The mothers of 174 prenatally DEX-exposed children (including 48 with CAH) and 313 unexposed children (including 195 with CAH) completed four standardized developmental questionnaires about their children. None of the comparisons of prenatally DEX-exposed children and unexposed controls was significant. Among the DEX-exposed children, increased duration of DEX exposure was correlated with significantly fewer developmental delays on three variables of one of the questionnaires, but none of the correlations reached significance, when Bonferroni corrections for multiple correlations were used. With the methods used, we were unable to document any adverse effects of early-prenatal DEX treatment in the doses recommended for the treatment of pregnancies at risk for CAH on motor and cognitive development. (J Clin
The Journal of Clinical Endocrinology & Metabolism, 2001
... S. Cabrera, Amanda Goseco, Karen Lin-Su, Andrea S. Putnam, J. Qing Wei and ... development of... more ... S. Cabrera, Amanda Goseco, Karen Lin-Su, Andrea S. Putnam, J. Qing Wei and ... development of pubic hair, insulin resistance, acne, reduced fertility, and, in women, polycystic ovaries ... As amniocentesis is performed in the second trimester, it is too late start dexamethasone ...
The Journal of Clinical Endocrinology & Metabolism, 1999
Archives of Sexual Behavior, 2004
Gender assignment of children with intersexuality and related conditions has recently become high... more Gender assignment of children with intersexuality and related conditions has recently become highly controversial. On the basis of extensive animal research and a few human case reports, some authors have proposed the putative masculinization of the brain by prenatal hormones—indicated by the degree of genital masculinization—as the decisive criterion of gender assignment and have derived the recommendation that 46,XX newborns with congenital adrenal hyperplasia (CAH) and full genital masculinization should be assigned to the male gender. The purpose of this study was to test in CAH girls of middle childhood the assumption that prenatal androgens determine the development of gender identity. Fifteen girls with CAH (range of genital Prader stage, 2–4/5), 30 control girls, and 16 control boys (age range, 5–12 years) underwent 2 gender-play observation sessions, and a gender identity interview yielding scales of gender confusion/dysphoria. About half a year earlier, mothers had completed 2 questionnaires concerning their children's gender-related behavior. The results showed that, as expected, CAH girls scored more masculine than control girls on all scales measuring gender-related behavior, with robust effect sizes. By contrast, neither conventionally significant differences nor trends were found on the 3 scales of the gender identity interview. We conclude that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior, but the absence of any increased gender-identity confusion/dysphoria does not indicate a direct determination of gender identity by prenatal androgens and does not, therefore, support a male gender assignment at birth of the most markedly masculinized girls.
Archives of Sexual Behavior, 2000
Gender assignment of children with intersexuality and related conditions has recently become high... more Gender assignment of children with intersexuality and related conditions has recently become highly controversial. On the basis of extensive animal research and a few human case reports, some authors have proposed the putative masculinization of the brain by prenatal hormones-indicated by the degree of genital masculinization-as the decisive criterion of gender assignment and have derived the recommendation that 46,XX newborns with congenital adrenal hyperplasia (CAH) and full genital masculinization should be assigned to the male gender. The purpose of this study was to test in CAH girls of middle childhood the assumption that prenatal androgens determine the development of gender identity. Fifteen girls with CAH (range of genital Prader stage, 2-4/5), 30 control girls, and 16 control boys (age range, 5-12 years) underwent 2 gender-play observation sessions, and a gender identity interview yielding scales of gender confusion/dysphoria. About half a year earlier, mothers had completed 2 questionnaires concerning their children's gender-related behavior. The results showed that, as expected, CAH girls scored more masculine than control girls on all scales measuring gender-related behavior, with robust effect sizes. By contrast, neither conventionally significant differences nor trends were found on the 3 scales of the gender identity interview. We conclude that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior, but the absence of any increased gender-identity confusion/dysphoria does not indicate a direct determination of gender identity by prenatal androgens and does not, therefore, support a male gender assignment at birth of the most markedly masculinized girls.
Journal of Steroid Biochemistry and Molecular Biology, 1999
The diagnostic term congenital adrenal hyperplasia (CAH) applies to a family of inherited disorde... more The diagnostic term congenital adrenal hyperplasia (CAH) applies to a family of inherited disorders of steroidogenesis caused by an abnormality in one of the five enzymatic steps necessary in the conversion of cholesterol to cortisol. The enzyme defects are translated as autosomal recessive traits, with the enzyme deficient in more than 90% of CAH cases being 21-hydroxylase. In the classical forms of CAH (simple virilizing and salt wasting), owing to 21-hydroxylase deficiency (21-OHD), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Non-classical 21-OHD (NC21OHD) refers to the condition in which partial deficiencies of 21-hydroxylation produce less extreme hyperandrogenemia and milder symptoms. Females do not demonstrate genital ambiguity at birth.The gene for adrenal 21-hydroxylase, CYP21, is located on chromosome 6p in the area of HLA genes. Specific mutations may be correlated with a given degree of enzymatic compromise and the clinical form of 21-OHD. NC21OHD patients are predicted to have mild mutations on both alleles or one severe and one mild mutation of the 21-OH locus (compound heterozygote). In most cases the mutation groups represent one diagnosis (e.g., Del/Del with SW CAH), however we have found several non-correlations of genotype to phenotype. Non-classical and classical patients were found within the same mutation group. Phenotypic variability within each mutation group has important implications for prenatal diagnosis and treatment.Prenatal treatment of 21-OHD with dexamethasone has been utilized for a decade. An algorithm has been developed for prenatal diagnosis and treatment, which, when followed closely, has been safe for both the mother and the fetus, and has been effective in preventing ambiguous genitalia in the affected female newborn. This is an instance of an inborn metabolic error successfully treated prenatally.Since 1986, prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) has been carried out in 403 pregnancies in The New York Hospital–Cornell Medical Center. In 280, diagnoses were made by amniocentesis, while 123 were diagnosed using chorionic villus sampling. Of the 403 pregnancies evaluated, 84 babies were affected with classical 21-OHD. Of these, 52 were females, 36 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 10 weeks of gestation (23 affected female fetuses) was effective in reducing virilization. Thirteen cases had affected female sibs (Prader stages 1–4); 6 of these fetuses were born with entirely normal female genitalia, while 6 were significantly less virilized (Prader stages 1–2) than their sibs, and one was Prader stage 3. Eight newborns had male sibs; 4 were born with normal genitalia, 3 were Prader stages 1–2, and 3 were born Prader stages 3–4. No significant or enduring side effects were noted in either the mothers or the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight, length, or head circumference from untreated, unaffected newborns.Based on our experience, proper prenatal diagnosis and treatment of 21-OHD is effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity of genital surgery, sex misassignment, and gender confusion.
Molecular Genetics and Metabolism, 2008
The Endocrinologist, 2003
... Update: Prenatal Diagnosis for Congenital Adrenal Hyperplasia in 595 Pregnancies. New, Maria ... more ... Update: Prenatal Diagnosis for Congenital Adrenal Hyperplasia in 595 Pregnancies. New, Maria I. MD; Carlson, Ann; Obeid, Jihad; Marshall, Ian; Cabrera, Monina S.; Goseco, Amanda; Lin-Su, Karen; Putnam, Andrea S.; Wei, J. Qing; Wilson, Robert C. ...
The Endocrinologist, 2003
ABSTRACT An abstract is unavailable. This article is available as HTML full text and PDF.
Molecular Genetics and Metabolism, 2007
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) occurs worldwide. T... more Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) occurs worldwide. The most common mutations in the CYP21A2 gene in 716 unrelated patients were analyzed and the mutations were grouped by ethnicity, as defined through self-declaration corroborated by review of pedigrees extending to two or three generations. Prevalent allelic mutations and genotypes were found to vary significantly among ethnic groups, and the predominance of the prevalent mutations and genotypes in several of these populations was significant. There are ethnicspecific mutations in the CYP21A2 gene. A large deletion is prevalent in the Anglo-Saxons; a V281L (1685 G to T) mutation is prevalent in Ashkenazi Jews; an R356W (2109 G to A) mutation is prevalent in the Croatians; an IVS2 AS -13 (A/C to G) mutation is prevalent in the Iranians and Yupik-speaking Eskimos of Western Alaska; and a Q318X (1994 C to T) mutation is prevalent in East Indians. Genotype/phenotype non-correlation was seen when at least one IVS2 AS -13 (A/C to G) mutation in the CYP21A2 gene was present.
Molecular Genetics and Metabolism, 2008
The Journal of Clinical Endocrinology & Metabolism, 2004
Dexamethasone (DEX) administration to the pregnant woman has become the treatment of choice for t... more Dexamethasone (DEX) administration to the pregnant woman has become the treatment of choice for the prevention of genital masculinization in female fetuses affected with congenital adrenal hyperplasia (CAH). Although no somatic teratological side effects have been found to date, recent animal research has shown adverse effects of glucocorticoids on brain structures such as the hippocampus, raising concerns about possible functional side effects of DEX on human development. The current survey of 487 children, 1 month to 12 yr of age, focused on cognitive and motor development. The mothers of 174 prenatally DEX-exposed children (including 48 with CAH) and 313 unexposed children (including 195 with CAH) completed four standardized developmental questionnaires about their children. None of the comparisons of prenatally DEX-exposed children and unexposed controls was significant. Among the DEX-exposed children, increased duration of DEX exposure was correlated with significantly fewer developmental delays on three variables of one of the questionnaires, but none of the correlations reached significance, when Bonferroni corrections for multiple correlations were used. With the methods used, we were unable to document any adverse effects of early-prenatal DEX treatment in the doses recommended for the treatment of pregnancies at risk for CAH on motor and cognitive development. (J Clin
The Journal of Clinical Endocrinology & Metabolism, 2001
... S. Cabrera, Amanda Goseco, Karen Lin-Su, Andrea S. Putnam, J. Qing Wei and ... development of... more ... S. Cabrera, Amanda Goseco, Karen Lin-Su, Andrea S. Putnam, J. Qing Wei and ... development of pubic hair, insulin resistance, acne, reduced fertility, and, in women, polycystic ovaries ... As amniocentesis is performed in the second trimester, it is too late start dexamethasone ...
The Journal of Clinical Endocrinology & Metabolism, 1999
Archives of Sexual Behavior, 2004
Gender assignment of children with intersexuality and related conditions has recently become high... more Gender assignment of children with intersexuality and related conditions has recently become highly controversial. On the basis of extensive animal research and a few human case reports, some authors have proposed the putative masculinization of the brain by prenatal hormones—indicated by the degree of genital masculinization—as the decisive criterion of gender assignment and have derived the recommendation that 46,XX newborns with congenital adrenal hyperplasia (CAH) and full genital masculinization should be assigned to the male gender. The purpose of this study was to test in CAH girls of middle childhood the assumption that prenatal androgens determine the development of gender identity. Fifteen girls with CAH (range of genital Prader stage, 2–4/5), 30 control girls, and 16 control boys (age range, 5–12 years) underwent 2 gender-play observation sessions, and a gender identity interview yielding scales of gender confusion/dysphoria. About half a year earlier, mothers had completed 2 questionnaires concerning their children's gender-related behavior. The results showed that, as expected, CAH girls scored more masculine than control girls on all scales measuring gender-related behavior, with robust effect sizes. By contrast, neither conventionally significant differences nor trends were found on the 3 scales of the gender identity interview. We conclude that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior, but the absence of any increased gender-identity confusion/dysphoria does not indicate a direct determination of gender identity by prenatal androgens and does not, therefore, support a male gender assignment at birth of the most markedly masculinized girls.
Archives of Sexual Behavior, 2000
Gender assignment of children with intersexuality and related conditions has recently become high... more Gender assignment of children with intersexuality and related conditions has recently become highly controversial. On the basis of extensive animal research and a few human case reports, some authors have proposed the putative masculinization of the brain by prenatal hormones-indicated by the degree of genital masculinization-as the decisive criterion of gender assignment and have derived the recommendation that 46,XX newborns with congenital adrenal hyperplasia (CAH) and full genital masculinization should be assigned to the male gender. The purpose of this study was to test in CAH girls of middle childhood the assumption that prenatal androgens determine the development of gender identity. Fifteen girls with CAH (range of genital Prader stage, 2-4/5), 30 control girls, and 16 control boys (age range, 5-12 years) underwent 2 gender-play observation sessions, and a gender identity interview yielding scales of gender confusion/dysphoria. About half a year earlier, mothers had completed 2 questionnaires concerning their children's gender-related behavior. The results showed that, as expected, CAH girls scored more masculine than control girls on all scales measuring gender-related behavior, with robust effect sizes. By contrast, neither conventionally significant differences nor trends were found on the 3 scales of the gender identity interview. We conclude that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior, but the absence of any increased gender-identity confusion/dysphoria does not indicate a direct determination of gender identity by prenatal androgens and does not, therefore, support a male gender assignment at birth of the most markedly masculinized girls.