172 research outputs found
Cytogenetic and molecular genetic investigations
No full textMale infertility and hypogonadism may be caused by a genetic defect, which should be investigated by cytoge-netic or molecular genetic analysis. The main indications for genetic testing in andrology are azoospermia and severe oligozoospermia. In selected cases of hypogonadotropic hypogonadism and Kallmann syndrome, especially those with an evident familial component, mutation screening of the known genes may be indicated. Even if detection of a genetic alteration will not substantially change the treatment, genetic testing should be performed for two reasons: (1) to finalize a causal diagnosis, and (2) to assess the genetic risk for the offspring in case of successful treatment. © 2010 Springer-Verlag Berlin Heidelberg
Diseases of the hypothalamus and the pituitary gland
No full textAmong males Kallmann syndrome in its fully developed form has a prevalence of about 1 in 10,000. The prevalence in males is four times higher than in females (Seminara et al. 1998). Currently the genetic defect underlying Kallmann syndrome and IHH can be demonstrated in about half of the familial cases and in about 10% of the sporadic cases. The old denomination idio-pathic hypogonadotropic hypogonadism, which reflects ignorance of the causal defect, therefore appears obsolete. The acronym IHH should stand for isolated hypogonadotropic hypogonadism, referring to the inadequacy of gonadotropin secretion as the only defect. © 2010 Springer-Verlag Berlin Heidelberg
Twenty-six novel EFNB1 mutations in familial and sporadic craniofrontonasal syndrome (CFNS)
No full textCraniofrontonasal syndrome (CFNS) is an X-linked disorder characterized by a more severe manifestation in heterozygous females than in hemizygous males. Heterozygous females have craniofrontonasal dysplasia (CFND) and occasionally extracranial manifestations including midline defects and skeletal abnormalities, whereas hemizygous males show no or only mild features such as hypertelorism and rarely show cleft lip or palate. Mutations in the EFNB1 gene in Xq12 are responsible for familial and sporadic CFNS. The EFNB1 gene encodes ephrin-B1, a transmembrane ligand that also exhibits receptor-like effects. We performed mutation analysis in nine unrelated families and 29 sporadic patients with CFNS. DNA sequencing revealed mutations in 33 (86.8%) cases including 26 distinct novel mutations. A recurrent nonsense mutation, c.196C>T/R66X, was detected in one family and four sporadic patients. The majority of mutations (26/33) were located in exons 2 and 3 of the EFNB1 gene encoding the extracellular ephrin domain. The mutation spectrum includes frameshift, nonsense, missense, and splice site mutations, with a predominance of frameshift and nonsense mutations resulting in premature truncation codons. For the first time we describe mutations in exons 4 and 5 of EFNB1. Of particular interest are the frameshift mutations located in the last 25 codons of EFNB1 encoding the carboxyterminal end of ephrin-B1. They result in an extension by 44 residues. These mutations disrupt the intracellular binding sites for Grb4 and PDZ-effector proteins involved in reverse signaling. We conclude that the major causes of familial as well as sporadic CFNS are loss of function mutations in the EFNB1 gene that comprise premature termination or abrogate receptor-ligand interaction, oligomerization, and ephrin-B1 reverse signaling.Wieland, Ilse ; Reardon, William ; Jakubiczka, Sibylle ; Franco, Brunella ; Kress, Wolfram ; Vincent‐delorme, Catherine ; Thierry, Patrick ; Edwards, Matt ; König, Rainer ; Rusu, Cristina ; Schweiger, Susann ; Thompson, Elizabeth ; Tinschert, Sigrid ; Stewart, Fiona ; Wieacker, Pete
Pseudotrisomy 13: Clinical findings and genetic implications
No full textThe combination of holoprosencephaly, postaxial polydactyly, and normal karyotype has been termed pseudotrisomy 13 syndrome. Here, we report the prenatal diagnosis of pseudotrisomy 13 in three siblings suggesting autosomal recessive inheritance of this syndrome. Clinical overlap with hydrolethalus syndrome, Smith-Lemli-Opitz syndrome, Meckel syndrome, and Pallister-Hall syndrome is discussed. Copyright (c) 2005 S. Karger AG, Basel
125. Les origines de la République romaine, neuf exposés suivis de discussions, par Einar Gjerstad, Frank E. Brown, P. J. Rii, Jacques Heurgon, Emilio Gabba, Krister Hanell, Arnaldo Momigliano, Andreas Alföldi, Franz Wieacker, J. H. Waszink, Denis van Berchem
No full textPetitmengin Pierre. 125. Les origines de la République romaine, neuf exposés suivis de discussions, par Einar Gjerstad, Frank E. Brown, P. J. Rii, Jacques Heurgon, Emilio Gabba, Krister Hanell, Arnaldo Momigliano, Andreas Alföldi, Franz Wieacker, J. H. Waszink, Denis van Berchem. In: Revue des Études Grecques, tome 81, fascicule 386-388, Juillet-décembre 1968. pp. 582-584
Acne resolution rates: Results of a single-blind, randomized, controlled, parallel phase III trial with EE/CMA (Belara (R)) and EE/LNG (Microgynon (R))
No full textBackground and Objective: Acne in women can often be successfully treated by the intake of oral contraceptives containing gestagens with anti-androgenic properties. This study aimed to evaluate the efficacy of the monophasic oral contraceptive ethinylestradiol/chlormadinone acetate (EE/CMA; Belara (R)) for the treatment of mild to moderate papulopustular acne of the face and acne-related disorders in comparison to EE/levonorgestrel (LNG; Microgynon (R)). Methods: 199 female acne patients were enrolled in a single-blind, randomized, multicentre phase III study and divided into two groups who received either EE/CMA or EE/LNG. The primary end point was fulfilled if the number of papules/pustules per half of the face present on admission had decreased by at least 50% in the 12th medication cycle. Results: 59.4% of the women under EE/CMA and 45.9% under EE/LNG were responders. The relative frequency of women with complete resolution was 16.5% under EE/CMA and 4.3% under EE/LNG at cycle 12. Conclusion: EE/CMA is an efficient treatment for women with mild and moderate papulopustular acne of the face and related disorders, reflecting the well-known anti-androgenic properties of the progestogen CMA. Copyright (C) 2001 S, Karger AG, Basel
Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome.
No full textA genetic origin is estimated in 30% of infertile men with the common phenotypes of oligo- or azoospermia, but the pathogenesis of spermatogenic failure remains frequently obscure. To determine the involvement of Copy Number Variants (CNVs) in the origin of male infertility, patients with idiopathic severe oligozoospermia (N = 89), Sertoli-cell-only syndrome (SCOS, N = 37)) and controls with normozoospermia (N = 100) were analysed by array-CGH using the 244A/400K array sets (Agilent Technologies). The mean number of CNVs and the amount of DNA gain/loss were comparable between all groups. Ten recurring CNVs were only found in patients with severe oligozoospermia, three only in SCOS and one CNV in both groups with spermatogenic failure but not in normozoospermic men. Sex-chromosomal, mostly private CNVs were significantly overrepresented in patients with SCOS. CNVs found several times in all groups were analysed in a case-control design and four additional candidate genes and two regions without known genes were associated with SCOS (P<1×10−3). In conclusion, by applying array-CGH to study male infertility for the first time, we provide a number of candidate genes possibly causing or being risk factors for the men's spermatogenic failure. The recurring, patient-specific and private, sex-chromosomal CNVs as well as those associated with SCOS are candidates for further, larger case-control and re-sequencing studies
Campomelic dysplasia without sex reversal in a Turkish patient is due to mutation Ala119Val within the SOX9 gene
No full textCampomelic dysplasia is a rare neonatal skeletal malformation syndrome mainly characterized by congenital boning and angulation of long bones in combination with other skeletal and estraskeletal defects. Two thirds of karyotypic males exhibit male-to-female ses reversal. Point mutations within SOX9 in 17q24-25 or rearrangements upstream to SOX9 as well as a deletion of a complete gene, causing haploinsufficiency of the gene product, have been detected in some patients. Recurrent mutations appear to be rare and most mutations detected in campomelic dysplasia are family specific. Here, we report on a Turkish patient with a 46,XY karyotype affected by campomelic dysplasia without sex reversal. Sequencing the SOX9 gene revealed a heterozygous Ala119Val mutation in exon 1, coding for the highly conserved HMG-box of the gene. This mutation is not present in the parents' lymphocyte DNAs. The same mutation was recently reported in a patient with 46,SX karyotype. Additionally, our patient is homozygous for the common polymorphism c507C-->T, while both parents are heterozygous. Clin Dysmorphol 10: 197-201 (C) 2001 Lippincott Williams & Wilkins
Localization of the gene for Wieacker Wolff syndrome in the pericentromeric region of the X chromosome
No full textContiguous gene deletions involving EFNB1, OPHN1, PJA1 and EDA in patients with craniofrontonasal syndrome.
No full textCraniofrontonasal syndrome (CFNS [MIM 304110]) is an X-linked malformation syndrome characterized by craniofrontonasal dysplasia and extracranial manifestations in heterozygous females. In the majority of patients CFNS is caused by mutations in the EFNB1 gene (MIM 300035). We identified three girls with classical CFNS and mild developmental delay harboring de novo deletions of the EFNB1 gene. Applying haplotype analysis, Southern blot hybridization and array-comparative genomic hybridization, deletion of EFNB1 was found to be part of contiguous gene deletions in the patients. In one patient the deletion interval includes the genes for oligophrenin-1 (OPHN1 [MIM 300127]) and praja 1 (PJA1 [MIM 300420]). In the second patient the deletion includes OPHN1, PJA1 and the gene for ectodysplasin A (EDA [MIM 300451]). In the third patient EFNB1 gene deletion may include deletion of regulatory regions 5' of OPHN1. Previously, the OPHN1 gene has been shown to be responsible for recessive X-linked mental retardation. Although it is too early to predict the future cognitive performance of the two infant patients with contiguous gene deletions of OPHN1-EFNB1-PJA1, mild learning disabilities have been recognized in the older, third patient. It is important for genetic counseling to be aware that their male offspring may not only be carriers of CFNS but may also be affected by mental retardation and anhidrotic ectodermal dysplasia
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