1/17. prenatal diagnosis of thoracopelvic dysplasia. A case report.BACKGROUND: Thoracopelvic dysplasia, a variant of asphyxiating thoracic dysplasia (Jeune syndrome), is an uncommon skeletal disorder characterized by a small thorax, pelvic abnormalities and other complex, combined anomalies, including hypomelia, polydactyly and renal anomalies. CASE: A 32-year-old woman, gravida 1, para 0, was referred at 27 weeks' gestation due to polyhydramnios. Sonography revealed hydramnios, low fetal thoracic circumference (TC) and abdominal circumference (AC) ratio (0.78), skull and skin edema, increased nuchal translucency (7 mm), micrognathia, low-set ears, left cardiac deviation (66 degrees), overriding fingers, and club and rock-buttock feet. amniocentesis revealed a normal karyotype (46, XY). Asphyxiating thoracic dysplasia was considered. At 40 weeks' gestation, a male infant was delivered vaginally. Besides the prenatal findings, cryptorchidism and high-arched palate were noted. radiography of the infant revealed a narrow, funnel-shaped thorax and small pelvis with short, flared iliac bones; poorly developed acetabulum; and small, shallow sciatic notch. No dyspnea was observed at five months postpartum. CONCLUSION: Thoracopelvic dysplasia should be considered when a low TC/AC ratio (< 0.8) is observed. In this case the final diagnosis was made after detailed exclusion of other disorders combined with observation of a small thorax. prenatal diagnosis of thoracopelvic dysplasia is possible.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
2/17. Loss of the SHOX gene associated with Leri-Weill dyschondrosteosis in a 45,X male.A male patient is reported with a 45,X karyotype and Leri-Weill dyschondrosteosis (LWD). FISH analysis with SHOX and SRY gene probes was carried out. One copy of both SHOX and SRY was detected in interphase nuclei, clarifying the origin of LWD and the male phenotype. Molecular results suggested that the 45,X karyotype arose through two independent events. The first occurred at paternal meiosis leading to an unequal crossing over between the short arms of the X and Y chromosomes. As a consequence, the SRY gene was translocated onto Xp, thereby explaining the male phenotype of the patient. The second event probably occurred at maternal meiosis or at the early stages of the zygote resulting in the loss of the maternal x chromosome.- - - - - - - - - - ranking = 2keywords = karyotype (Clic here for more details about this article) |
3/17. Greenberg dysplasia: first reported case with additional non-skeletal malformations and without consanguinity.In 1988 Greenberg et al. reported an association of fetal hydrops with irregular calcification and moth-eaten skeletal dysplasia. Here, we report on the first case of this disorder accompanied by additional malformations (omphalocele, intestinal malrotation, disturbed fingernails and toes, hypolobated lungs) in a German couple without consanguinity (karyotype 46,XY). Sonograpically, the fetus was characterised by tetraphokomelia, severe generalised hydrops, pulmonal hypoplasia and hepato-splenomegaly. Greenberg dysplasia should be considered in differential diagnosis in cases with severe fetal hydrops and phokomelia on antenatal sonography.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
4/17. Leri-Weill syndrome associated with a pseudodicentric X;Y translocation chromosome and skewed X-inactivation: implications for genetic counselling.A female patient of normal intelligence with short stature and Madelung deformity is reported with Leri-Weill dyschondrosteosis and a de novo pseudodicentric X;Y translocation chromosome. The phenotype is consistent with the observed deletion of the SHOX gene by FISH and molecular studies. The y chromosome breakpoint was in the short arm but proximal to SRY, consistent with her phenotypic sex. X-inactivation studies have shown a skewed pattern in favour of the dic (X;Y) chromosome. The ARSE gene was also deleted on the dic (X;Y) chromosome but chondrodysplasia punctata was not expressed, as CDP is recessive and ARSE escapes inactivation on the normal x chromosome. Breakpoint mapping assisted in karyotype/phenotype correlation and reproductive counselling. In particular, molecular analysis showed that the putative MRX 49 gene for mental retardation is unlikely to be deleted in this case.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
5/17. campomelic dysplasia without sex reversal in a Turkish patient is due to mutation Ala119Val within the SOX9 gene.campomelic dysplasia is a rare neonatal skeletal malformation syndrome mainly characterized by congenital bowing and angulation of long bones in combination with other skeletal and extraskeletal defects. Two thirds of karyotypic males exhibit male-to-female sex 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,XX karyotype. Additionally, our patient is homozygous for the common polymorphism c507C-->T, while both parents are heterozygous.- - - - - - - - - - ranking = 2keywords = karyotype (Clic here for more details about this article) |
6/17. A man who inherited his SRY gene and Leri-Weill dyschondrosteosis from his mother and neurofibromatosis type 1 from his father.We report on a man with neurofibromatosis type 1 (NF1) and Leri-Weill dyschondrosteosis (LWD). His father had NF1. His mother had LWD plus additional findings of turner syndrome (TS): high arched palate, bicuspid aortic valve, aortic stenosis, and premature ovarian failure. The proband's karyotype was 46,X,dic(X;Y)(p22.3;p11.32). Despite having almost the same genetic constitution as 47,XXY klinefelter syndrome, he was normally virilized, although slight elevation of serum gonadotropins indicated gonadal dysfunction. His mother's karyotype was mosaic 45,X[17 cells]/46,X,dic(X;Y)(p22.3;p11.32)[3 cells].ish dic(X;Y)(DXZ1 ,DYZ1 ). The dic(X;Y) chromosome was also positive for Y markers PABY, SRY, and DYZ5, but negative for SHOX. The dic(X;Y) chromosome was also positive for X markers DXZ1 and a sequence < 300 kb from PABX, suggesting that the deletion encompassed only pseudoautosomal sequences. Replication studies indicated that the normal X and the dic(X;Y) were randomly inactivated in the proband's lymphocytes. LWD in the proband and his mother was explained by SHOX haploinsufficiency. The mother's female phenotype was most likely due to 45,X mosaicism. This family segregating Mendelian and chromosomal disorders illustrates extreme sex chromosome variation compatible with normal male and female sexual differentiation. The case also highlights the importance of karyotyping for differentiating LWD and TS, especially in patients with findings such as premature ovarian failure or aortic abnormalities not associated with isolated SHOX haploinsufficiency.- - - - - - - - - - ranking = 2keywords = karyotype (Clic here for more details about this article) |
7/17. Molecular characterization of partial trisomy 16q24.1-qter: clinical report and review of the literature.We describe a 3(1/2)-year-old girl with psychomotor and mental retardation; dysmorphic features, including a high forehead with bitemporal narrowing; a broad nasal bridge and a broadened nose; downslanting palpebral fissures; abnormal ears; vertebral abnormalities; cardiac defect; genital hypoplasia; and anal abnormalities. The karyotype of our patient (550 bands) was normal. Molecular cytogenetic techniques, including comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH), revealed that this girl was a carrier of a de novo derivative chromosome 7 arising from a cryptic t(7;16)(p22.3;q24.1) translocation generating a trisomy 16q24.1-qter and a 7p22.3-pter deletion. FISH with a series of specific chromosome 7p and 16q probes allowed us to delineate the chromosome 7 breakpoint between YAC660G6 (WD7S517) and YAC848A12 (D7S521, D7S31, and WI-4829) and the chromosome 16 breakpoint between BAC457K7 (D42053) and BAC44201 (SGC30711). The comparison of the clinical features of our patient with those of 2 cases of pure terminal 7p deletion and 28 cases of trisomy 16q reported in the literature allowed us to establish the following phenotype-genotype correlation for trisomy of the long arm of chromosome 16: distinctive facies (high/prominent forehead, bitemporal narrowing, periorbital edema in the neonatal period); severe mental retardation; vertebral, genital, and anal abnormalities to 16q24; distal joint contractures and camptodactyly to 16q23; cleft palate and renal anomalies to 16q22; beaked nose and gall bladder agenesis to 16q21; gut malrotation; lung and liver anomalies to 16q13; and behavior abnormalities to band 16q11-q13.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
8/17. Variable expression of campomelic dysplasia in a father and his 46, XY daughter.campomelic dysplasia (CD, MIM 114290) is characterised by widespread osseous abnormalities including bowing of the long bones, dysplasia of the cartilage of the tracheobronchial tree, and neurological abnormalities leading to high perinatal lethality. A majority of karyotypic males present as phenotypic females. The disorder has only recently been categorised as a dominantly transmitted entity after demonstration of heterozygous mutations in the SOX9 gene on chromosome 17q24.3 or translocations associated with breakpoints upstream of this gene. Despite this mode of transmission, only two well-documented instances of parent-child transmission of the disorder have been described. We report a man of normal intelligence with mild phenotypic and radiological appearances of CD. His first-born child, a phenotypic female with a 46,XY karyotype, presented with significantly more severe skeletal and neurological involvement. parents of individuals with CD should be examined for minimal manifestations of the disorder, which may represent phenotypic variability in the syndrome or somatic mosaicism.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
9/17. New autosomal recessive chondrodysplasia--pseudohermaphrodism syndrome.Two siblings with a previously undescribed syndrome are presented. They both have severe dwarfism, antenatal in origin, with generalized chondrodysplasia, severe microcephaly with cerebellar vermis hypoplasia, a hypoplastic iris and a papillous coloboma (coloboma of the optic disc). The first sibling has a 46,XY karyotype despite normal female internal and external genitalia. She has moderate mental retardation. Gestation of the second sibling was interrupted after antenatal diagnosis. The fetus was 46,XX and very similar to the first case.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
10/17. An Xp; Yq translocation causing a novel contiguous gene syndrome in brothers with generalized epilepsy, ichthyosis, and attention deficits.PURPOSE: We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri-Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the x chromosome. methods: physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement. RESULTS: The subjects had generalized epilepsy, X-linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative x chromosome. Deleted distal Xp genes included short-stature homeobox on the x chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X-chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1 , KAL , STS-, SHOX-) mat. CONCLUSIONS: Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes.- - - - - - - - - - ranking = 2keywords = karyotype (Clic here for more details about this article) |
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