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Katrin Ounap

Publications and source records attributed to Katrin Ounap.

13 recordsLinked to original sources
PubMed2006

Prevalence of Angelman syndrome and Prader-Willi syndrome in Estonian children: sister syndromes not equally represented.

In 2000-2004, we performed a focused search for individuals with Angelman syndrome (AS) and Prader-Willi syndrome (PWS) aiming to establish the prevalence data for the individuals born between 1984 and 2004 in Estonia. All persons with probable AS or PWS (n = 184) were studied using the DNA methylation test. Individuals with abnormal methylation were all further tested by chromosomal and FISH analysis, and if necessary for uniparental disomy and UBE3A gene mutation. Nineteen cases with abnormal methylation test result were identified. Seven of them had AS, including six (85.7%) due to 15q11-13 deletion and one paternal UPD15. Twelve subjects had PWS: 4 (33%) 15q11-13 deletions, 6 (50%) maternal UPD15, 1 unbalanced chromosome 14;15 translocation resulting in a chromosome 15pter-q13 deletion, and 1 Robertsonian 15q;15q translocation. The minimum livebirth prevalence in 1984-2004 for AS was 1:52,181 (95% CI 1:25,326-1:1,29,785) and for PWS 1:30,439 (95% CI 1:17,425-1:58,908). The livebirth prevalence of AS and PWS increased within this period, but the change was statistically significant only for PWS (P = 0.032), from expected 1:88,495 (95% CI 1:24,390-1:3,22,580) to expected 1:12,547 (95% CI 1:540-1:29,154). Six individuals with AS and 11 with PWS were alive on the prevalence day (January 1, 2005), indicating the point prevalence proportion of 1:56,112 (95% CI 1:25,780-1:1,52,899) and 1:30,606 (95% CI 1:17,105-1:61,311), respectively. Our results showing the birth prevalence of AS 1.7 times less than PWS challenge the opinion that both syndromes are equally represented, and are in line with the view that mutations in sperm and oocytes occur at different frequencies.

Angelman Syndrome↗
PubMed2006

Characterization of two supernumerary marker chromosomes in a patient with signs of Klinefelter syndrome, mild facial anomalies, and severe speech delay.

A boy with signs of Klinefelter syndrome, mild facial dysmorphic features, and severely retarded speech development displayed a female karyotype with mosaicism for two marker chromosomes 48,XX,+mar1,+mar2[68]/47,XX,+mar1[19]/47,XX,+mar2[6]/46,XX[8]. Using chromosomal microdissection, locus-specific fluorescence in situ hybridization (FISH), and PCR with several Y-chromosome markers, the larger supernumerary marker chromosome (SMC) was characterized as a ring Y-chromosome. Detection of the SRY-region explained the male phenotype. The smaller second marker chromosome contained the pericentromeric region of chromosome 8. We suggest that the co-occurrence of a partial Y-chromosome and partial trisomy 8 explain the severe speech delay and the facial dysmorphic features.

Abnormalities, Multiple↗
PubMed2006

Descriptive epidemiology of Down's syndrome in Estonia.

The aim of the study was to investigate the livebirth prevalence of Down's syndrome (DS) in Estonia during the past 14 years, create a DS database and observe the effectiveness of prenatal screening. This is a population-based descriptive study. The study subjects were children with DS diagnosis born between the years 1990 and 2003. We collected data from genetic centres in Estonia, from the databases of DS support groups, from institutions for disabled children and from the registers of family doctors/paediatricians. Prenatal screening for chromosomal anomalies for women aged >or=35 years was started in Estonia in 1995. Therefore, we divided the DS children into two groups: 112 born between 1990 and 1994 comprise group I, and 127 born between 1995 and 2003 comprise group II. Group II was further divided into two subgroups: IIa, from 1995 to 1998, when screening of advanced maternal age (>or=35 years) commenced, and IIb, from 1999 to 2003, when screening of second trimester maternal serum for younger women commenced. Prenatally, 68 cases of DS were diagnosed between 1995 and 2003 in the whole of Estonia, and all of these pregnancies were terminated. This represents 34.9% of all delivered and prenatally detected DS cases from this period. The overall livebirth prevalence was 1.17 per 1000 livebirths. The livebirth prevalence in group I was 1.25 and in group II was 1.09 per 1000 livebirths. The second trimester maternal serum screening with advanced maternal age screening was more effective than advanced maternal age screening alone. The livebirth prevalence in group IIa was 1.22 and in group IIb 0.99 per 1000 livebirths. Overall, regular trisomy was found in 90.4%, translocation in 6.3% and mosaicism in 2.9%. The overall male to female sex ratio of DS was 1.09.

Adult↗
PubMed2005

A new case of 2q duplication supports either a locus for orofacial clefting between markers D2S1897 and D2S2023 or a locus for cleft palate only on chromosome 2q13-q21.

We report on a pure duplication of the proximal chromosome 2q in a 6.5-year-old boy with V-shaped midline cleft palate and bifid uvula, posteriorly located tongue, and micrognathia (Pierre Robin sequence), celiac disease, failure to thrive, and developmental delay. Cytogenetic and FISH analysis indicated a duplication of chromosome 2q13-q22. In general, pure proximal duplication or triplication of 2q is rare. The clinical features and chromosomal breakpoints of the 10 previously reported patients varied, and no common phenotype or proximal duplication/triplication 2q syndrome could be defined to date. However, based on four previous patients with different orofacial clefts and our case, a locus for orofacial clefting may be located at proximal 2q. The duplication/triplication comprised chromosome 2q13 in all five affected individuals including our patient. Our patient and three previous cases (two with cleft palate only (CPO) and one with cleft lip/palate (CL/P)) showed a cytogenetic breakpoint at 2q13, which could support the presence of a critical dominant gene disrupted by a common breakpoint, however, the fifth case with CPO showed different breakpoints, advocating against the disruption of a critical dominant gene and supporting that the overexpression of a gene(s) on chromosome 2q13-q21 may cause cleft palate only (CPO) and Pierre Robin sequence. Hence, our findings support either the presence of one locus for orofacial clefting (CL/P, CPO, and Pierre Robin sequence) between markers D2S1897 (chromosome 2q12.2) and D2S2023 (chromosome 2q14.2), or alternatively the presence of a locus for CPO and Pierre Robin sequence on chromosome 2q13-q21.

Abnormalities, Multiple↗
PubMed2005

A girl with inverted triplication of chromosome 3q25.3 --> q29 and multiple congenital anomalies consistent with 3q duplication syndrome.

We report a newborn girl with intrachromosomal triplication of 3q25.3 --> q29 (mosaicism) who died at the age of 3.5 weeks due to her malformations. She demonstrated disproportionate short stature with short limbs, a prominent and hairy forehead, thick eyebrows, synophrys, small upturned nose, full cheeks, micrognathia, and low set malformed and posteriorly rotated ears, short and webbed neck, hydrocephalus, Dandy-Walker malformation, spina bifida, complex heart defect (ventricular and atrial septal defect, malrotation, and interrupted aortic arch), omphalocele, polycystic kidneys, postaxial polydactyly of left hand, and generalized hirsutism; all signs have been associated with the dup(3q) syndrome previously. The facial appearance (hairy forehead, thick eyebrows, synophrys, small upturned nose, full cheeks, micrognathia, low set malformed and posteriorly rotated ears) showed resemblance to the Brachmann-de Lange syndrome (BDLS), but the patient did not fulfill the diagnostic criteria for BDLS. There has been only one report of a direct triplication of chromosome 3 until now, but in our case the triplicated area is larger, located more proximally, and includes the hypothetical BDLS critical gene region-CDL1. Our findings lend support to distal chromosome 3q, or chromosome 3q26.3, comprises the critical area for the dup(3q) phenotype resembling the BDLS.

Abnormalities, Multiple↗
PubMed2005

MECP2 mutation analysis in patients with mental retardation.

Mutations in the methyl-CpG-binding protein 2 (MECP2) gene are known to underlie Rett' syndrome, the most common cause of mental retardation (MR) in girls. Since the original report, phenotypes resulting from MECP2 mutations have been shown to extend, for example, to several Rett variants, autism, atypical Angelman syndrome, and nonspecific MR. It was earlier proposed that MECP2 mutations might account for approximately 2% of the male cases with nonspecific MR. Thereby, the frequency of MECP2 mutations in the mentally retarded population would be comparable to that of Fragile-X syndrome. The aim of this study was to analyze well-characterized cases with MR and to clarify the role of the MECP2 gene in the etiology of MR and atypical Angelman syndrome. The coding sequence of the MECP2 gene was analyzed in a sample of 118 patients (103 males, 15 females) by direct sequencing. Two coding sequence variants, 602C > T (A201V) and 1189G > A (E397K), were identified. In addition, we identified four variants in the intronic or 3'UTR regions. None of these variants is likely to be causal. We conclude that the evidence across all the mutation screening studies implies that MECP2 mutations do not represent a major cause of nonspecific MR.

Chromosomal Proteins, Non-Histone↗
PubMed2005

A female with Angelman syndrome and unusual limb deformities.

This report presents the case of a 13-year-old female with Angelman syndrome caused by 15q11-13 microdeletion demonstrating unusual marked limb deformities with generalized osteoporosis, delayed bone age, and brachydactyly type B. The radiographs of her femur, tibia, fibula, ulna, and radius revealed curved deformities in the distal diaphysis-metaphysis areas and generalized osteoporosis. This can be explained by the patient's severe disability, delayed puberty, presumed nutritional and environmental deficits, or rickets. In addition, she had shortening of the distal phalanges of all fingers, the absence of some epiphyses of the distal phalanges, and hypertrophic and curved III metacarpal bones. These clinical findings could not be explained by classical rickets or osteoporosis, but can be classified as brachydactyly type B. To our knowledge, such marked limb deformities and brachydactyly have not previously been described in patients with Angelman syndrome.

Adolescent↗
PubMed2004

Two sisters with Silver-Russell phenotype.

Silver-Russell syndrome (SRS) is a well recognizable syndrome, but the etiology of SRS seems to be heterogeneous. SRS is listed in Mendelian Inheritance in Man as an autosomal dominant disorder because most described cases have been of sporadic occurrence, and most likely were caused by de novo autosomal dominant mutation, and because families with apparent dominant transmission of a SRS phenotype have been described. Still, in a few families, autosomal recessive inheritance has been suggested. We describe two sisters who meet the criteria for SRS proposed by Price et al. [1999]. The parents had normal facial features, normal height, and normal post-natal growth. This is the second well-documented case of familial recurrence of SRS that resembles an autosomal recessive inheritance pattern. Since sib recurrence is so rare in SRS, other modes of inheritance should be considered. The finding of maternal uniparental disomy 7 (mUPD7) in 10% of SRS cases suggests that lack of paternally expressed imprinted gene(s) or overexpression of maternal imprinted gene(s) on chromosome 7 cause SRS. The recurrence in sibs could be caused by a mutation in the imprinted gene or imprinting center carried by one parent. Alternatively, recurrence in sibs could represent germ line mosaicism for a dominant mutation in one of the parents.

Abnormalities, Multiple↗
PubMed2004

Subtelomere FISH in 50 children with mental retardation and minor anomalies, identified by a checklist, detects 10 rearrangements including a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33.

Submicroscopic or subtle aneusomies at the chromosome ends, typically diagnosed by subtelomere fluorescence in situ hybridization (FISH), are a significant cause of idiopathic mental retardation (MR). Some 20 subtelomere studies, including more than 2,500 subjects, have been reported. The studies are not directly comparable because different techniques and patient ascertainment criteria were used, but an analysis of 14 studies showed that aberrations were detected in 97 out of 1,718 patients (5.8%, range 2-29%; 95% confidence interval (CI) 4.60-6.84%). We performed a subtelomere FISH study of 50 unrelated children ascertained by a checklist that evaluates MR or developmental delay, dysmorphism, growth defect, and abnormal pedigree and found 10 bona fide causal rearrangements (detection rate 20%, 95% CI 10-33.7%). The findings included five unbalanced familial translocations or inversions, two unbalanced de novo translocations, and two de novo deletions. Patient 5 showed multiple anomalies (large head, vision defect, omphalocele, heart defect, enlarged kidneys, moderate MR, speech defect, mild transient homocysteinemia) and a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33. The report of a subtelomeric balanced rearrangement associated with a disease phenotype is a novel one. FISH mapping using panels of overlapping BAC clones identified a number of candidate genes at or near his breakpoints, including ASPA, TRPV3, TRPV1, and CTNS at 17p13.3, and three genes of unknown function at 20q13.33. Only the homocysteinemia could be speculatively linked to one of these genes (CTNS, the gene for cystinosis). Three within the subset of 16 children (18.8%) with mild (IQ, 50-69) or unspecified degree of MR tested positive, suggesting that the checklist approach could be especially useful within this group of patients.

Adolescent↗
PubMed2003

DiGeorge/velocardiofacial syndrome: FISH studies of chromosomes 22q11 and 10p14, and clinical reports on the proximal 22q11 deletion.

DiGeorge anomaly/velocardiofacial syndrome (DG/VCFS) occurs with different deletion intervals on chromosomes 22q11, while the DiGeorge anomaly (with other findings) is seen in patients with deletions of 10p14. The clinical outcome with the common 22q11 deletion (90% of cases) is well known, but the outcome with the less frequent deletion types has not been well documented. Using cytogenetic and fluorescence in situ hybridization (FISH) analysis we studied a series of 295 patients with suspected DG/VCFS. We identified 58 subjects with a 22q11 deletion, and none with a 10p deletion. Fifty-two subjects had the common deletion, five had the proximal deletion, and one had an atypical proximal deletion due to a 1;22 translocation. We report clinical data of four subjects with the proximal 22q11 microdeletion, and of one patient with the atypical proximal deletion. The anomalies observed with the proximal 22q11 microdeletion fell within the DG/VCFS spectrum. Two females, 6 and 25 years old, had normal mental development. Normal development has been reported with the common 22q11 deletion, but only in a minority of cases. This study may indicate a better intellectual and/or behavioral outcome with the proximal vs. the common 22q11 deletion, rather than a chance finding.

Abnormalities, Multiple↗
PubMed2003

Parents' satisfaction with medical and social assistance provided to children with Down syndrome: experience in Estonia.

OBJECTIVE: Parents of children with mental or physical disabilities have been assumed to live more stressful lives than other parents, and people with Down syndrome (DS) may get second-rate care because of their diagnosis. The aim of this work is to investigate the extent of parents' satisfaction with medical and social services in Estonia provided for the DS individuals and their families. METHODS: From 1999 to 2001, fifty-nine DS families answered questionnaires in which we inquired about their satisfaction with medical and social assistance. RESULTS: We found that satisfaction with the quality of the information about DS is low, and most of the parents are not satisfied with the social benefits and rehabilitation options. CONCLUSIONS: The DS families need more medical information about this syndrome. The medical staff has to learn more about how to deliver bad news and how to support parents. More work needs to be done in the area of rehabilitation options and social assistance.

Down Syndrome↗
PubMed2002

Girl with combined cellular immunodeficiency, pancytopenia, malformations, deletion 11q23.3 --> qter, and trisomy 8q24.3 --> qter.

We describe here a 3-year-old girl demonstrating combined cellular immunodeficiency of B- and T-cells, pancytopenia, multiple anomalies, and severe mental retardation. Cytogenetic analysis and fluorescent in situ hybridization (FISH) indicated an unbalanced translocation of chromosomes 8q and 11q, resulting in monosomy 11q23.3-qter and trisomy 8q24.3-qter. The association of cellular immunodeficiency and partial deletion 11q and/or partial trisomy 8q has not been described previously; however, the 11q deletion has been reported with humoral immunodeficiency or pancytopenia. Some one-third to one-half of patients with partial monosomy 11q were reported to have pancytopenia, which has been related to the absence of the 11q23-q24 region. Our case narrows down the critical interval for thrombo- or pancytopenia to 11q23.3-q24 and excludes both the ATM (which resides on 11q23.1) and the MLL genes as possible candidate genes. We are proposing that haploinsufficiency of the NFRKB gene on 11q24-q25 and/or the ETS-1 proto-oncogene on 11q24 may have caused or contributed to the immunodeficiency (decreased levels of B- and T-lymphocytes) in our patient.

Abnormalities, Multiple↗