196 research outputs found
Genotype versus phenotype in families with androgen insensitivity syndrome
Androgen insensitivity syndrome encompasses a wide range of phenotypes,
which are caused by numerous different mutations in the AR gene. Detailed
information on the genotype/phenotype relationship in androgen
insensitivity syndrome is important for sex assignment, treatment of
androgen insensitivity syndrome patients, genetic counseling of their
families, and insight into the functional domains of the AR. The commonly
accepted concept of dependence on fetal androgens of the development of
Wolffian ducts was studied in complete androgen insensitivity syndrome
(CAIS) patients. In a nationwide survey in The Netherlands, all cases (n =
49) with the presumptive diagnosis androgen insensitivity syndrome known
to pediatric endocrinologists and clinical geneticists were studied. After
studying the clinical phenotype, mutation analysis and functional analysis
of mutant receptors were performed using genital skin fibroblasts and in
vitro expression studies. Here we report the findings in families with
multiple affected cases. Fifty-nine percent of androgen insensitivity
syndrome patients had other affected relatives. A total of 17 families
were studied, seven families with CAIS (18 patients), nine families with
partial androgen insensitivity (24 patients), and one family with female
prepubertal phenotypes (two patients). No phenotypic variation was
observed in families with CAIS. However, phenotypic variation was observed
in one-third of families with partial androgen insensitivity resulting in
different sex of rearing and differences in requirement of reconstructive
surgery. Intrafamilial phenotypic variation was observed for mutations
R846H, M771I, and deletion of amino acid N682. Four newly identified
mutations were found. Follow-up in families with different AR gene
mutations provided information on residual androgen action in vivo and the
development of the prepubertal and adult phenotype. Patients with a
functional complete defective AR had some pubic hair, Tanner stage P2, and
vestigial Wolffian duct derivatives despite absence of AR expression.
Vaginal length was functional in most but not all CAIS patients. The
minimal incidence of androgen insensitivity syndrome in The Netherlands,
based on patients with molecular proof of the diagnosis is 1:99,000.
Phenotypic variation was absent in families with CAIS, but distinct
phenotypic variation was observed relatively frequent in families with
partial androgen insensitivity. Molecular observations suggest that
phenotypic variation had different etiologies among these families. Sex
assignment of patients with partial androgen insensitivity cannot be based
on a specific identified AR gene mutation because distinct phenotypic
variation in partial androgen insensitivity families is relatively
frequent. In genetic counseling of partial androgen insensitivity
families, this frequent occurrence of variable expression resulting in
differences in sex of rearing and/or requirement of reconstructive surgery
is important information. During puberty or normal dose androgen therapy,
no or only minimal virilization may occur even in patients with
significant (but still deficient) prenatal virilization. Wolffian duct
remnants remain detectable but differentiation does not occur in the
absence of a functional AR. In many CAIS patients, surgical elongation of
the vagina is not indicated
Vermeersch (A.) en Wouters (H.). Bijdragen tot de geschiedenis van de Belgische pers, 1830-1848
De Vroede M. Vermeersch (A.) en Wouters (H.). Bijdragen tot de geschiedenis van de Belgische pers, 1830-1848. In: Revue belge de philologie et d'histoire, tome 37, fasc. 3, 1959. Langues et littératures modernes — Moderne talen en letterkunden. pp. 827-830
La Formation des maîtres en Europe jusqu'en 1914
De Vroede Maurice. La Formation des maîtres en Europe jusqu'en 1914. In: Histoire de l'éducation. n° 6, 1980. pp. 35-46
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