bluuebunny/crossref_metadata_2025 huggingface dataset:
11q trisomy detected by fluorescence in situ hybridization
Authors: Takano Takako , Yamanouchi Yasuko , Kawashima Shoko , Date Masatsune , Hashira Shintaro , Kida Mitsushiro , Abe Toshiaki , Nakahori Yutaka , Nakagome Yasuo
Published: July 2010

Takano T, Yamanouchi Y, Kawashima S, Date M, Hashira S, Kida M, Abe T, Nakahori Y, Nakagome Y. 11q trisomy detected by fluorescence in situ hybridization. Clin Genet 1993: 44: 324–328. © Munksgaard, 1993

A patient with psychomotor developmental delay, multiple minor anomalies, congenital heart disease and left inguinal hernia is reported. His karyotype was 45,X/46,X,+mar (3 : 37 cells), and the marker chromosome was identified as t(Y;11) (q12;q14?) using fluorescence in situ hybridization and fluorescent chromosome painting. He was diagnosed as mosaic for de novo 11q trisomy.
Disease profile of 400 institutionalized mentally retarded patients in Kuwait
Authors: Farag T. I. , Al‐Awadi S. A. , El‐Badramary M. H. , Aref M. A. , Kasrawi B. , Murthy D. S. Krishna , El‐Khalifa M. Y. , Yadav G. , Marafie M. J. , Bastaki L. , Wahba R. A. , Mohammed F. M. , Hassan S. Abul , Redha A. A. , Redha M. A. , Al‐Aboud H. , Al‐Hijji S. , Al‐Dighashem D. , Al‐Hashash N. , Al‐Jeryan L. , Al‐Khorafi H. , Qurban E. A. , Al‐Sulaiman I.
Published: July 2010

Farag TI, Al‐Awadi SA, El‐Badramary MH, Aref MA, Kasrawi B, Krishna Murthy DS, El‐Khalifa MY, Yadav G, Marafie MJ, Bastaki L, Wahba RA, Mohammed FM, Abul Hasan S, Redha AA, Redha MA, Al‐aboud H, Al‐Hijji S, Al‐Dighashem D, Al‐Hashash N, Al‐Jeeryan L, Al‐Khor‐afi H, Qurban EA, Al‐Sulaiman I. Disease profile of 400 institutionalized mentally retarded patients in Kuwait.

Clin Genet 1993: 44: 329–334. © Munksgaard, 1993

In this preliminary report we summarize the results of a 4‐year multidisciplinary systematic, etiological clinicogenetic survey of 400 institutionalized mentally retarded patients in Kuwait. All had an intelligence quotient below 50. A constitutional disorder, as the direct cause of the mental retardation, was found in 203 patients (50.75%)): a chromosomal abnormality in 37 (9.25%), Mendelian disorders in 137 (34.25%), MCA/MR in 22 (5.55%) and CNS malformations in 7 cases (1.75%). In 157 patients (39.35%) a pre‐, peri or postnatal cause was ascertained. No etiological diagnosis was detected in 40 patients (10%). A detailed analysis of the “disease profile” is given and compared with the results of previous diagnostic genetic surveys among different institutionalized mentally retarded populations in Western and developing countries.
Erythrocyte membrane cation carrier in Down syndrome
Authors: Naylor G. J. , Semple M. , Irvine E. A.
Published: July 2010

Erythrocyte sodium pump was estimated in subjects with Down syndrome and in matched mentally handicapped controls: there was no significant difference in measures of sodium pump between the two groups.
Guadalajara camptodactyly syndrome type I. A corroborative family
Authors: Figuera L. E. , Ramírez‐Dueñas M. L. , Garcia‐Cruz D. , Villar V. , Cantú J. M.
Published: July 2010

Three sibs, two girls aged 18 and 9 years, and a 7‐year‐old boy, were found to have Guadalajara camptodactyly syndrome type I (GCSI). They had intrauterine growth retardation, dwarfism, peculiar facial appearance, camptodactyly and skeletal anomalies. Comparison with other camptodactyly syndromes led to the conclusion that the patients had the same disorder as the two first reported patients with GCSI. The clinical and radiological concordance in the five patients permits further delineation of GCSI and corroboration of its autosomal recessive inheritance.
Characterization of a deleted Y chromosome in a male with Turner stigmata
Authors: Calzolari E. , Patracchini P. , Palazzi P. , Aiello V. , Ferlini A. , Trasforini G. , Uberti E. Degll , Bernardi F.
Published: July 2010

A 46,X, + mar karyotype was detected in an 11‐year‐old male with a clinical picture characterized by obesity, short stature, bilateral cryptorchidism and coarctation of the aorta. The presence of ZFY and SRY genes was demonstrated by PCR amplification, and the origin of the marker chromosome from a deleted Y chromosome was analyzed by in situ hybridization. The proximal limits of a deletion in Yq were defined by the absence of Southern blot hybridization signals upon probing with Yql 1 markers. Cytogenetics and molecular methods taken together indicate a deletion in q11.21. In addition, the loss of Yp subtelomeric sequences was suggested by the analysis of Southern blots hybridized with a 29A24 (DXYS14) probe and by the presence of coarctation of the aorta tentatively localized in Yp. The karyotype of the patient was suggested to be: 46,X,del(Y)(p11.3‐qll.21).
Familial occurrence of hereditary renal adysplasia with Müllerian anomalies
Authors: Battin Jacques , Lacombe Didier , Leng Jean‐Joël
Published: July 2010

We report on a family with unilateral or bilateral renal agenesis and Müllerian anomalies (vaginal atresia or minor anomalies). This family provides support for an autosomal dominant pattern of inheritance with incomplete penetrance and variable expressivity in hereditary renal adysplasia (HRA) associated with Müllerian defects.
A case of a female infant with simultaneous occurrence of de novo terminal deletions on chromosome 14q and 20p
Authors: Uehara S. , Akai Y. , Takeyama Y. , Okamura K. , Takabayashi T. , Yajima A. , Natsui M. , Nakai H.
Published: July 2010

This is a case report on an infant with de novo terminal deletions on the long arm of chromosome 14 and on the short arm of chromosome 20 [46, XX, del(14)(q32)del(20)(p11)]. Examination revealed that the infant had a peculiar face, a cleft and high palate, abnormal dentition, butterfly‐like vertebral defects, finger anomalies, a simian line on the left hand, talipes equinovarus, deep plantar furrows, abnormally high values of alkali phosphatase and lactate dehydrogenase, mild anemia and psychomotor retardation. Comparing the present case with previously reported cases of a single deletion on chromosome 14q or chromosome 20p, the infant showed some symptomatic and dysmorphic features of both deletions.
Heritable unstable DNA sequences and hypermethylation associated with fragile X syndrome in Japanese families
Authors: Hori Tada‐aki , Yamauchi Masatake , Seki Naohiko , Tsuji Satsuki , Kondo Ikuko
Published: July 2010

Fragile X syndrome, associated with the fragile site at Xq27.3 (FRAXA), is the most common form of familial mental retardation. The fragile X mutation has recently been characterized as a heritable unstable DNA sequence, p(CCG)n/p(CGG)n, in the FRAXA locus. In the present study, a correlation between fragile X‐genotypes in the FRAXA locus and hypermethylation of an adjacent CpG island was examined in four Japanese families with fragile X syndrome. We show here that the heritable unstable DNA sequences in the fragile X chromosome usually increase in size when transmitted by female carriers, and that the degree of methylation in the CpG island correlated with the increased sizes of the unstable DNA sequences. When a hypermethylated full mutation was transmitted by a male to his daughters, both the size of the unstable DNA sequence and the degree of the methylation reduced to the premutation range. Our observations suggest that female meiosis has a greater potential for amplifying unstable DNA sequences and that amplified DNA sequences can be transmitted through germ cells, while male germ cells seem not to be able to tolerate highly amplified unstable DNA sequences.
Attitudes of Dutch general practitioners towards presymptomatic DNA‐testing for Huntington disease
Authors: Thomassen René , Tibben Aad , Niermeijer Martinus F. , van der Does Emiel , van de Kamp Jacques J. P. , Verhage Frans
Published: July 2010

The attitudes of 1020 Dutch GP's towards presymptomatic and prenatal testing for Huntington disease (HD) were studied by means of a postal questionnaire. The questionnaire contained questions about: approval of presymptomatic DNA‐testing, informing individuals at‐risk who do not request predictive testing, referral to a clinical genetics center, and opinions about different strategies of informing and supporting individuals at‐risk. The response rate was 62%. More than two‐thirds of the GP's considered post‐test counselling and support as their responsibility. Twenty‐six per cent were of the opinion that the test results should be disclosed by the GP. Fifty‐nine per cent of GP's who had an individual at‐risk in their practice were familiar with the test. The attitudes of GP's towards giving support and giving test results were independent of familiarity with the test and the incidence of HD‐patients or at‐risk individuals in the practice. Although GP's were willing to play an important role in presymptomatic DNA‐testing procedures, there is a risk that they might underestimate the difficulties in communicating genetic information and the psychosocial effects of DNA‐testing. Hence, we favor the premise that extensive pretest counselling and test disclosure should remain the prime responsibility of the clinical geneticist. Increasing involvement of GP's should, however, be encouraged and combined with appropriate postgraduate education about predictive DNA‐testing in general.
Hyperkeratosis‐hyperpigmentation syndrome: a confirmative case
Authors: Figuera L. E. , Rodriguez‐Catellanos M. A. , Gonzalez‐Mendoza A. , Cantú J. M.
Published: July 2010

A 22‐year‐old female showing hyperpigmented spots and mild palmoplantar hyperkeratosis as leading features is presented. The diagnosis of Hyperkeratosis‐hyperpigmentation syndrome, previously described by our group as an autosomal dominant trait, was unmistakable, thus permitting the corroboration of this genodermatosis.
46,XY del(18) (q21.3q22.2) with mosaicism of r(18) and a milder form of the 18q— syndrome
Authors: Maaswinkel‐Mooij P. D. , de Jong P. , Beverstock G. C.
Published: July 2010

A mosaic karyotype: 46, XY, del(18) (q21.3q22.2)/47, XY, del(18) (q21.3q22.2) + marker, was found in a mentally retarded male with a mild form of the 18q— syndrome and aplasia of the right thumb. By fluorescent in situ hybridisation, the marker chromosome could be identified as a ring chromosome no. 18.
Multipoint linkage analysis in X‐linked juvenile retinosclusis
Authors: Bergen A. A. B. , Van Schooneveld M. J. , Orth U. , Bleeker‐Wagemakers E. M. , Gal A.
Published: July 2010

Thirteen families with X‐linked juvenile retinoschisis (XLRS) were studied in order to evaluate the linkage relationship between the XLRS locus (RS) and seven X‐chromosomal DNA markers. Linkage was found between RS and DXS9 (max = O.11, Zmax = 4.17), DXS16 (θmax = 0.06, Zmax = 7.72), DXS41 (θmax = 0.06, Zmax = 8.13) and DXS43 (θmax = 0.03, Zmax = 6.11). Recombinants were found between RS and all loci studied. Multipoint linkage analysis and recombination analysis significantly favour the order of Xpter‐(DXS9, (DXS16‐DXS43))‐RS‐DXS41 ‐Xcen.
Nager acrofacial dysostosis: minor familial manifestations supporting dominant inheritance
Authors: Bonthron David T. , Macgregor Donald F. , Barr David G. D.
Published: July 2010

We report on a girl with Nager acrofacial dysostosis, three of whose relatives had variable mild anomalies of the thumb. The possible relationship of such minor features to the radial limb anomalies in the proposita provides further evidence that the Nager syndrome can be the manifestation of a dominantly inherited disorder with very variable expressivity.
Del(2q) — cause of the wrinkly skin syndrome?
Authors: Kreuz Friedmar R. , Wittwer Birbei H.
Published: July 2010

We report the cases of a mother and her two sons with de1(2) (q32). Their phenotypes are compared with those of 20 individuals reported previously in the literature. All described cases apparently have identical deletions. Common manifestations include small size at birth, retarded growth and development, craniofacial dysmorphism and skeletal and ocular anomalies. Our patients also have symptoms of the wrinkly skin syndrome (WSS), which is characterized by the wrinkling of the abdominal skin and of the skin of the dorsum of the hands and feet, decreased elastic recoil of the skin, an increased number of palmar and plantar creases, musculoskeletal anomalies, microcephaly, mental retardation and an old appearance. Our three patients show a striking pattern in skin biopsies when viewed by light microscopy, and a peculiar grimacing was noted in the boys. Their serum copper and caeruloplasmin levels are slightly raised.
Identification of the chromosome 14 origin of a C‐negative marker associated with a 14q32 deletion by chromosome painting
Authors: Sacchi Ivana Magnani Nicoletta , Darfler Marlene , Nisson Paul E. , Tornaghi Raffaella , Fuhrman‐Contl Anna Maria
Published: July 2010

A constitutional chromosome 14 rearrangement was observed in a female with a psychodevelopmental disorder. Karyotype analysis using a variety of chromosome techniques, QFQ, GTG, CBG, Ag‐NOR and DA‐DAPI, showed a deletion of chromosome 14q32.1‐qter region in association with a supernumerary marker chromosome. The marker, resembling a submetacentric, approximately half the size of a G group chromosome is C band and Ag‐NOR negative. The heteromorphism of the satellites showed that the deleted chromosome 14 is paternal in origin. Chromosome painting using an Alu‐PCR probe specific for the human chromosome 14 and fluorescent in situ hybridization (FISH) showed that the marker contains chromosome 14q32 sequences. It is likely that the marker was generated from the deleted chromosome 14 region through a complex rearrangement.
Can cytomegalovirus cause brachydactyly? A case report and review of the literature
Authors: Cinbis M. , Topcu M. M. D. , Balcl S.
Published: July 2010

A child with the diagnosis of CMV infection associated with brachydactyly is presented. The case is interesting as, to our knowledge, no similar case has been reported up to the present. In our case, apart from CMV, no teratogenic factor which may cause brachydactyly could be detected.
A new simple and rapid dual assay for AFP and free β hCG in screening for Down syndrome
Authors: Nørgaard‐Pedersen Bent , Alfthan Henrik , Arends Jørgen , Høgdall Claus K. , Larsen Severin Olesen , Pettersson Kim , Stenman Ulf‐Håkan , Salonen Riitta
Published: July 2010

We have evaluated a simple and rapid 2‐step dual‐label assay (DELFIA®) for alphafetoprotein (AFP) and free β subunit of human gonadotropin (hCGβ) in second‐trimester screening for Down syndrome. Based on stored serum samples from 1059 normal control pregnancies and 72 cases of Down syndrome, we have found the mean Multiple of Median (MoM) for AFP and free hCGβ to be 0.70 and 2.31, respectively. This is slightly but not significantly better than the values for the separate assay for AFP (0.76 MoM) and for intact hCG (2.11 MoM). However, the dual assay is much simpler than the separate assays and therefore prospective comparison trials should be carried out.
Congenital myopathy with fiber type disproportion: a family with a chromosomal translocation t(10; 17) may indicate candidate gene regions
Authors: Gerdes Anne Marie , Petersen Michael B. , Schrøder Henrik D. , Wulff Karl , Brøndum‐Nielsen Karen
Published: July 2010

A patient with myopathy and congenital fiber type disproportion presented at birth with arthrogryposis multiplex congenita, dislocation of the hips and mild scoliosis. Later in life she developed marked muscle weakness. A balanced chromosomal translocation t(10;17) (p11.2;q25), transmitted by the clinically healthy mother, who nevertheless showed discrete signs of myopathy, was demonstrated. DNA analysis excluded maternal uniparental disomy for loci on both chromosomes 10 and 17. We suggest that the translocation breakpoints are candidate regions for a myopathy gene.
Exclusion of an elastin gene (ELN) mutation as the cause of pseudoxanthoma elasticum (PXE) in one family
Authors: Raybould M. C. , Birley A. J. , Moss C. , Hultén M. , McKeown C. M. E.
Published: July 2010

An intragenic elastin Hint I polymorphism has been used to study the inheritance of elastin alleles in a family considered to show recessive inheritance of pseudoxanthoma elasticum (PXE). The marker has proved informative, excluding the elastin gene as a cause of PXE in this family. In addition, whole genomic human elastin clones were used in Southern analysis to screen the family for gross elastin gene rearrangements, but none were detected.
An 87 bp deletion in exon 5 of the LDL receptor gene in a mother and her son with familial hypercholesterolemia
Authors: Schlüter Gregor , Wick Ursula
Published: July 2010

DNA analysis of the low density lipoprotein receptor (LDLR) gene was performed in two persons with familial hypercholesterolemia (FH). Southern blot experiments indicated the heterozygous loss of an EcoRI site in exon 5 of the LDLR gene. Upon amplification and sequencing of exon 5 in both probands, an 87‐bp deletion in a heterozygous state could be evaluated. This is a novel mutation, most probably leading to the formation of a nonfunctional LDLR. Analysis of the deletion breakpoints revealed the presence of a six‐base‐pair consensus sequence 5′TGA/GA/GG/TA/C3′, which is characteristic of small deletions in different genetic defects.
The gene for familial dystonia with myoclonic jerks responsive to alcohol is not located on the distal end of 9q
Authors: Wahlström J. , Ozelius L , Kramer P. , Kyllerman M. , Schuback D. , Forsgren L. , Holmgren G. , Drugge U. , Sanner G. , Fahn S. , Breakefield X. O.
Published: July 2010

A gene (DYT1) for susceptibility to early‐onset torsion dystonia in Ashkenazi Jewish and Gentile kindreds is situated on chromosome 9q32‐q34 in a 6–7 cM span between markers AK1 and ASS. To determine whether transmission of familial dystonia with myoclonic jerks responsive to alcohol was consistent with a gene in this region, we studied the 37 members of a Swedish family, of whom 20 were so affected. A lod score of < −2.00 from a two‐point linkage analysis with six DNA markers covering a 30 cM span from D9S26 to D9S10 that included the region of the DYT gene indicated that this gene is not located in this region, and that two or more autosomal loci are responsible for hereditary dystonia in humans.
A new human mtDNA polymorphism: tRNAGln/4336 (T→C)
Authors: Leroy David , Nerby Seren
Published: July 2010

We report the observation of a polymorphism in the human mitochondrial tRNAGln gene. This polymorphism is detectable by both NlaIII and Sau96I, whose recognition sequences overlap at the polymorphic base pair.
Ethnic differences in the occurrence of the M1(ala213) haplotype of alpha‐1‐antitrypsin in asthmatic and non‐asthmatic black and white South Africans
Authors: Gaillard M. C. , Zwi S. , Nogueira C. M. , Ludewick H. , Feldman C. , Frankel A. , Tsilimigras C. , Kilroe‐Smith T. A.
Published: July 2010

An ethnic study of 175 individuals, comprising 65 black and 110 white South Africans, has shown a conclusive difference in the frequency of the M1(ala213) haplotype of α1‐antitrypsin (P < 0.00001). The M1(ala213) haplotype occurred more frequently in the black group. In the latter group, the frequency of the M1(ala213) haplotype was the same in both controls (0.55) and asthmatics (0.53). However, there was a significant difference in the frequencies (0.19 and 0.36) for the respective white groups (P < 0.01), the frequency of the M1(ala213) haplotype being much higher in the asthmatics. Apart from the above differences, there was also a difference in the elastase‐inhibitory capacities of the homozygote phenotypes M1(val213) vs M1(ala213) (P < 0.0001), this capacity being lower in the latter phenotype. We conclude that the occurrence of the M1(ala213) allele of α1‐antitrypsin differs in various ethnic groups and may play a role in asthma.
Informativity of intragenic microsatellites for carrier detection and prenatal diagnosis of cystic fibrosis in the Italian population
Authors: Magnani C. , Cremonesi L. , Belloni E. , Ferrari M. , Seia M. , Russo M. P. , Devoto M. , Ronchetto P. , Romeo G.
Published: July 2010

Molecular diagnosis of cystic fibrosis (CF) in the Italian population, based on the detection of the deltaF508 mutation (51.2% of CF chromosomes), provides full informativity for prenatal diagnosis (PDN) in about 28% of families at risk. Identification of the predominant non‐deltaF508 mutations allows the characterization of about 70% of CF chromosomes, making approximately 48% of couples fully informative. In families where at least one chromosome remains uncharacterized, allele segregation is still determined using RFLPs closely linked to the CF gene. The recent identification of three polymorphic clusters of dinucleotide repeats (IVS8/ GT, IVS17b/TA and IVS17b/CA) led us to evaluate whether their analysis might improve feasibility studies for prenatal diagnosis or hetero‐zygote identification. One hundred nuclear families with a CF child, reflecting the general Italian deltaF508 mutation distribution, were geno‐typed for the three microsatellites. In this study microsatellite analysis using IVS8/GT and IVS17b/TA allowed the identification of both parental CF chromosomes in 94% of couples; inclusion in the study of the less polymorphic repeat locus, IVS17b/CA, slightly improved this percentage (97%). Hence, a strategy involving primarily the detection of the delta F508 mutation and secondarily microsatellite analysis makes possible PDN of CF in virtually all Italian CF families.
No effect of insertion/ deletion polymorphism at the ACE locus on normal blood pressure level or variability
Authors: Berge K. E. , Berg K.
Published: July 2010

Angiotensin I‐converting enzyme (ACE) cleaves angiotensin I to angiotensin II, which is the active component in the renin‐angiotensin system (RAS). We have studied an insertion/deletion polymorphism in DNA at the ACE locus. In three different series comprising 140, 90 and 136 unrelated individuals we found no evidence of association between genotypes in this insertion/deletion (I/D) polymorphism and level of systolic or diastolic blood pressure. In two series of 130 and 88 monozygotic (MZ) twin pairs, respectively, there was no difference between genotypes in within‐pair variation in systolic or diastolic blood pressure. Thus, in these series of healthy people, neither “level gene” nor “variability gene” effects of this insertion/deletion polymorphism were observed.
Multiple coagulation defects and the Cohen syndrome
Authors: Schlichtemeier Tammi L. , Tomlinson Gail E. , Kamen Barton A. , Waber Lewis J. , Wilson Golder N.
Published: July 2010

A 13‐year‐old male presented with new onset seizures, sagittal sinus thrombosis with cerebral hemorrhage, and extensive venous thrombosis of the lower limbs. Laboratory investigation demonstrated combined deficiency of protein C, protein S, and antithrombin III. He and his 17‐year‐old sister had a mental retardation‐multiple anomaly syndrome associated with microcephaly, unusual facies, and lax connective tissue. Their dysmorphology included elongated faces with narrow forehead, arched eyebrows, large mouth with down‐turned corners, malformed teeth, and furrowed tongue. Both had Marfanoid habitus with lax joints, pectus excavatum, kyphoscoliosis, and flat narrow feet. The most likely diagnosis for these siblings is the autosomal recessive Cohen syndrome of mental retardation, congenital hypotonia with Marfanoid habitus, microcephaly, pleasant affect, micrognathia, and open mouth with prominent incisors. The sagittal sinus thrombosis, left frontal intracranial hemorrhage, carotid aneurysm, tortuous descending aorta, and deep venous thrombosis suffered by the male sibling adds the Cohen syndrome to genetic vasculopathies that may be associated with stroke.
Two transthyretin mutations (glu42gly, his90asn) in an Italian family with amyloidosis
Authors: Skare James , Junes Lee Anna , Myles Noelle , Kane Kelly , Milunsky Aubrey , Cohen Alan , Skinner Martha
Published: July 2010

A family with familial amyloidotic polyneuropathy (FAP) was previously found to have a substitution of asparagine for histidine at position 90 of transthyretin. Members with his90asn developed FAP. However, close examination of the transthyretin gene revealed that glu42gly is coinheri‐ted with his90asn in this family. Since glu42gly has already been seen in Japanese FAP patients, and his90asn has been found in Portuguese and German individuals without FAP, we conclude that his90asn is a nonpathogenic variant.
Plasminogen with type‐I mutation in the Chinese Han population
Authors: Li Liming , Kikuchi Shuichi , Arinami Tadao , Kohayashi Kimiko , Tsuchiya Shigeru , Hamaguchi Hideo
Published: July 2010

A functionally inactive plasminogen (PLG) variant, PLG M5, is polymorphic in the Japanese population and has a codon 601 mis‐sense mutation (GCT for Ala to ACT for Thr), designated type‐I mutation. The present study aimed to reveal whether the plasminogen with type‐I mutation is present in the Chinese Han population. Among 104 healthy Chinese students, phenotype PLG AM5 was found in three subjects (2.9%), while 100 subjects were phenotype A and one was phenotype AA3. In the three subjects with PLG AM5, plasma concentrations of immunoreactive PLG were normal but PI G activities were decreased. Analysis using PCR and dot‐blot hybridization with allele‐specific oligonucleotide probes revealed the presence of the type‐I mutation in the PLG gene of all three subjects with PLG AM5. The data indicate that PLG with type‐I mutation is present in the Chinese Han population, possibly at a polymorphic frequency.
Inbreeding and congenital heart diseases in a North Indian population
Authors: Badaruddoza  , Afzal Mohd. , Akhtaruzzaman
Published: July 2010

The study was performed in six mohallahs (colonies) of Aligarh City (North India). All six mohallahs are predominantly inhabited by Qureshi (meat sellers, a highly endogamous group) Muslims. A total of 1721 infants and children up to the age of 6 years were examined to determine the incidence of congenital heart diseases (CHD) in relation to the degree of consanguinity of the parents. Around 43% of the subjects were the offspring of consanguineous marriages including second‐cousin, first‐cousin‐once‐removed and first‐cousin. A higher percentage of CUD was found in the offspring of consanguineous marriages: about 3.37% out of 741 children as compared to 1.22% in 980 offspring of non‐consanguineous marriages, whereas in the first‐cousin offspring, the percentage of CHD rose to 4.41%. The differences were found to be statistically significant. The present study suggests a genetic influence and also casts doubt on the applicability of a polygenic threshold model to all forms of cardiac malformation.
X‐linked recessive nephritis with mental retardation, sensorineural hearing loss, and macrocephaly
Authors: Robson W. Lane M. , Lowry R. Brian , Leung Alexander K. C.
Published: July 2010

A family with hereditary nephritis, sensorineural hearing loss, macrocephaly, and mental retardation is reported. X‐linked recessive inheritance was suggested by the presence of two affected brothers and a maternal uncle. This association may be a previously unreported variant of Alport's syndrome.
Macrocephaly, distinct craniofacial appearance and spastic paraplegia: an autosomal recessive subtype of complicated spastic paraplegia
Authors: Fryns J. P. , Hellemans M. , Van den Berghe H.
Published: July 2010

In this report we describe two siblings, a 15‐year‐old female and her 8‐year‐old brother, with spastic paraparesis, macrocephaly and distinct craniofacial appearance, as an apparent autosomal recessive subtype of complicated spastic paraplegia.
DNA carrier detection in X‐linked progressive cone dystrophy
Authors: Bergen A. A. B. , Meire F. , Schuurman E. J. M. , Delleman J. W.
Published: July 2010

X‐linked progressive cone dystrophy (XLPCD) is characterized by progressive macular atrophy, abnormal colour vision, reduced cone responses in ERG, and reduced visual acuity. XLPCD may be genetically heterogeneous. Therefore, carrier detections by DNA analysis may only be carried out in those families in which the position of the gene locus can be clearly established. Here, we describe the first DNA carrier detections in XLPCD.
Umbilical findings in Aarskog syndrome
Authors: Tsukahara Masato , Fernandez G. Isabel
Published: July 2010

We report on five patients with Aarskog syndrome who show previously undescribed umbilical features. Two of the five patients had protruding umbilicus, while the other three had a characteristic umbilicus consisting of a smooth depression with radiating branches of the cicatrix, and a flat cushion. These umbilical configurations have not previously been described in association with Aarskog syndrome. The flat configuration of the umbilicus could be a characteristic umbilical finding associated with Aarskog syndrome as well as the protruding umbilicus.
Mild phenotype and normal gonadal function in females with 4p trisomy due to unbalanced t(X;4)(p22.1;p14)
Authors: Petit Paul , Hilliker Carl , Van Leuven Fred , Fryns Jean‐Pierre
Published: July 2010

In this report we describe the mild phenotypic manifestations and normal gonadal function in a 50‐year‐old mother and her 17‐year‐old daughter with 4p trisomy resulting from an unbalanced t(X;4)(p22.1;p14) mat. Late replication of the der(X) was demonstrated by BrdU incorporation with spreading of the late replication to the 4p portion as an explanation of the reduced effect of the trisomy 4p/monosomy Xp on the physical and secondary sexual development in both patients.
Down syndrome associated with systemic lupus erythematosus: a mere coincidence or a significant association?
Authors: Bakkaloglu Aysin , Ozen Seza , Besbas Nesrin , Saatci Umit , Balci Sevim
Published: July 2010

An 8‐year‐old male, who had Down syndrome associated with systemic lupus erythematosus (SLE), is described. He also had a partial complement 4 deficiency. This case is a reminder that the physician should be aware of the possibility of an immune defect in a male presenting with SLE at a young age. The question of whether the association of Down syndrome with SLE is coincidental or whether there is a predilection for autoimmune disorders in Down syndome is discussed.
Down syndrome and male fertility: PCR‐derived fingerprinting, serological and andrological investigations
Authors: Zühlke Christine , Thies Ulrike , Braulke Ingrid , Reis André , Schirren Carl
Published: July 2010

Down syndrome, the most common birth defect causing mental retardation, is characterized by a specific phenotype including subfertility or sterility and hypogonadism in males. In contrast, several females with Down syndrome have borne offspring. Here, a male with trisomy 21 fathering an infant is described. This observation is verified by serological markers, DNA fingerprinting using different DNA micro‐or minisatellites and andrological investigations.
Etiological subgroups in non‐syndromic isolated cleft palate. A genetic‐epidemiological study of 52 Danish birth cohorts
Authors: Christensen Kaare , Fogh‐Andersen Poul
Published: July 2010

Isolated cleft palate (CP) is considered to be a heterogeneous trait with an important genetic contribution to the etiology. Multifactorial‐threshold models of non‐syndromic CP inheritance assume a female predominance. The present study of 52 Danish birth cohorts, using several ascertainment sources, identified 2301 CP cases. It was found that, although females tended to be more severely affected than males, the overall sex ratio was close to one. For the latter half of the study period (1962‐87), which probably had the best ascertainment, the sex ratio for non‐syndromic CP was 0.95 (95% C.I. 0.85‐1.07). Marked difference in sex ratios for non‐syndromic overt CP including the hard palate (CPH) and non‐syndromic overt CP of the soft palate only (CPS) (0.69 vs 1.00, p<1.00, p<0.05) suggested that these two conditions may be etiologically distinct, a hypothesis which is embryologically plausible. In agreement with this hypothesis, Danish family data from surgically treated CP cases showed a strong tendency to segregate only one of the CP subtypes within families. Future studies are recommended to test the existence of a possible etiological difference between CPH and CPS.
Familial translocation (X;3) (p22.3;p23): chromosomal in situ suppression (CISS) hybridization and inactivation pattern study
Authors: Bettio D. , Rizzi N. , Giardino D.
Published: July 2010

High‐resolution chromosome banding and chromosomal in situ suppression hybridization were used to identify a derivative X in a 10‐month‐old female patient with congenital heart defect and slight dysmorphism. The unbalanced karyotype was monosomic for Xp22.3‐pter and trisomic for 3p23 ‐pter regions. The derivative X was inherited from the mother carrier of a balanced translocation (X;3) (p22.3;p23). Replication study of the patient showed the abnormal X,t(X;3) to be late replicating, except for the translocated segment. This patient demonstrated only epicanthus and congenital heart defect, despite her partial trisomy 3. The clinical phenotype may be less severe when the X‐chromosome is involved in an unbalanced translocation.
Patient with de novo 12p+ syndrome identified as dir dup (12) (p13) using subchromosomal painting libraries from somatic cell hybrids
Authors: Zelante L. , Calvano S. , Dallapiccola B. , Mingarelli R. , Antonacci R. , Chiovato L. , Rocchi M.
Published: July 2010

Several patients with partial 12p duplications are known. An additional patient, who presented with the clinical manifestations of trisomy 12p syndrome, is described. De novo duplication 12p13.1 →pter was diagnosed using subchromosomal painting libraries obtained from somatic cell hybrids.
Antley‐Bixler syndrome: report of a patient and review of literature
Authors: Hassell Sarah , Butler Merlin G.
Published: July 2010

We report a patient with Antley‐Bixler syndrome and review 13 patients from the literature. The cardinal features of this condition include craniosynostosis, severe mid‐face hypoplasia, proptosis, choanal atresia/stenosis, frontal bossing, dysplastic ears, depressed nasal bridge, radiohumeral synostosis, long‐bone fractures and femoral bowing, urogenital abnormalities and a normal karyotype. Early death was identified in 54% of the reported cases, usually due to respiratory complications. The oldest patient at the time of follow up was 10 years of age. Intellectual performance has been variable (developmental testing of our patint at 30 months of age showed a range of developmental skills equivalent to 6 to 11 months of age). Chronic respiratory distrees, especially if accompanied by periods of apnea, may be important in the causation of mental retardation. Some patients with the syndrome have normal itelligence, which suggests a normally developing brain, particularly if a craniectomy is performed to treat sutural synostosis and idicates that there may be secondary factors (e.g., apnea) plaing a role in the mental retardation (as seen in our patient with a history of apnea) in patients with the Antley‐Bixer syndrome. Since choanal atresia/stenosis which diminishes the airway passage is a cardinal feature of this syndrome, choanal stenting shoule be performed on those patients with this finding during infancy to decrease the airway obstruction. All patients followed beyond infancy were ambulatory, including our patient at 35 months of age, who will take steps with assistance. Although most cases are sporadic, there were reports of recurrence in siblings of both sexes in two families, suggesting an autosomal recessive mode of inheritance.
Studies on the structure and function of the apolipoprotein(a) gene
Authors: Byrne Christopher D. , Lawn Richard M.
Published: July 2010

Lp(a) is an LDL‐like lipoprotein that is a major inherited risk factor for atherosclerosis. It is distinguished from Lp(a) by the addition of apolipoprotein(a). The gene structure of apolipoprotein(a) is homologous to plasminogen, and competition with plasminogen activity may account for some of the pathophysiology associated with Lp(a). Six highly related genes have now been identified, and at least four are found in close proximity in overlapping genomic clones. Studies have begun on the regulation of apolipoprotein (a) gene expression, and the human apolipoprotein(a) gene has been inserted into transgenic mice, where it leads to the development of arterial lesions.
Importance of Lp(a) lipoprotein and HLA genotypes in atherosclerosis and diabetes
Authors: Dahlén Gösta H. , Slunga Lisbeth , Lindblom Bertil
Published: July 2010

Lp(a) lipoprotein [Lp(a)] was found in previous studies to be independently associated with early atherosclerosis and its sequelae. Lp(a) in vitro bound to glucosaminoglycans and was easily aggregated at physiological Ca2+ concentration, and small Lp(a) aggregates were phagocytosed by macrophages. Lp(a) was also found to be related to carbohydrate metabolism, and increased Lp(a) levels have been described in diabetic patients with clinical complications and were recently found in rheumathoid arthritis patients. In this study of nondiabetic male patients with documented CAD before 50 years of age and controls, a significant correlation was found between Lp(a) and IGF‐1 levels. HLA class II DR13 (DR6) was more frequent and DR15 (DR2) was less frequent in patients than in controls. The calculated relative risk for CAD was 4.0 for DR17 (DR3), but the difference was not significant. These differences seem to be related to high Lp(a) levels. It is suggested that phagocytosis of preferably Lp(a) aggregates can induce an immunological tissue response that may contribute in the pathogenesis of Lp(a)‐associated diseases and may be more prominent in combination with some inherited HLA class II haplotypes. Probably due to sex hormone effects, the association may be most pronounced in young males and in older females.
High Lp(a) lipoprotein level in maternal serum may interfere with placental circulation and cause fetal growth retardation
Authors: Berg Kåre , Roald Borghild , Sande Hans
Published: July 2010

We report on a woman with an Lp(a) lipoprotein level above the 99th centile of the population distribution of concentrations, who at the age of 43 had had deep vein thrombosis causing a pulmonary embolus and whose brother, who also had a very high level, had suffered a cerebral infarction at the age of 43. She had given birth to three children, all with very low birth weight, one of whom died when 3 months old. The placentas had been small and ischemic. The concurrence of a very high Lp(a) lipoprotein level, familial thromboembolic disease and recurrent placental ischemia with delivery of children with low birth weight suggests the possibility that a very high Lp(a) lipoprotein concentration may predispose to placental insufficiency, presumably arising from pathological changes in maternal uterine vessels in the placental bed. If confirmed, a very high Lp(a) lipoprotein level may be a factor to consider in women who have repeated pregnancies with placental insufficiency and who give birth to children with low birth weight.
Mice transgenic for the human LCAT gene
Authors: Mehlum Anja , Prydz Hans
Published: July 2010

The enzyme LCAT (Lecithin:cholesterol acyltransferase E.C. 2.3.1.43.) plays a central role in lipoprotein metabolism. It is secreted by the liver and catalyzes the transfer of a fatty acid from the 2‐position of lecithin to the 3‐beta‐OH group of free cholesterol to produce cholesterol ester and lysolecithin.
Colorectal cancer: lessons for genetic counselling and care for families
Authors: Müller Hansjakoh , Scott Rodney , Weber Walter , Meier Remy
Published: July 2010

Cancers of the colon and the rectum are the second leading cause of malignacy in European countries with similar incidence rates for men and women and, therefore, one of the major health concerns. Emphasis is placed on the early detection of a developing neoplasm in order to improve the life expectancy of patients and their quality of life. Colorectal cancer (CRC) is an excellent model for studying the etiology and pathogenesis of a common malignancy and the complex multistage process of carcinogenesis. Abundant clinical and pathological evidence suggests that CRC arises from benign adenomas that proceed through a series of steps to metastatic carcinomas. Following the discovery of oncogenes and, more importantly tumor suppressor genes, Fearon & Vogelstein (1990) proposed a scheme of genetic events which are associated with colorectal tumorigenesis. Genetic linkage studies have recently identified another type of gene for colon cancer susceptibility that seems to act by destabilising the genome.
Heredity in personality disorders — an overview
Authors: Dahl Alv A.
Published: July 2010

The concept of personality disorders is based on deviant personality traits in both the DSM‐III‐R and ICD‐10 classifications. A diagnosis of personality disorder can be made reliably with structured interviews. Many individuals are diagnosed with more than one personality disorder, and other mental disorders are often found at the same time. Among the 11 personality disorders in DSM‐III‐R, only the schizotypal, borderline, and antisocial have been examined to any considerable extent for gene effects. The problems of studying heredity are here demonstrated for borderline and antisocial personality disorders. Recommendations are given as to strategies for further study of heredity in personality disorders.
Adults with Williams‐Beuren syndrome: evaluation of the medical, psychological and behavioral aspects
Authors: Plissart L. , Borghgraef M. , Volcke Ph. , Van den Berghe H. , Fryns J. P.
Published: July 2010

In order to evaluate the medical, psychological and behavioral aspects of Williams‐Beuren syndrome in adulthood, data were collected on 11 patients aged 17 to 66 years. The medical data did not confirm previous reports of significant morbidity. All adults were found to have a moderate or severe degree of mental handicap. They showed the same psychological profile as found in children: good verbal abilities, poor motor abilities, problems with sequencing and with performance tasks. The adults we evaluated showed little disturbing behavior in comparison to other mentally retarded subjects. They achieved a good level of autonomy. The majority lived at home with one or both parents and attended a day centre.
Predictive testing for Huntington disease: social characteristics and knowledge of applicants, attitudes to the test procedure and decisions made after testing
Authors: Holloway Susan , Mennie Moira , Croshie Aileen , Smith Brian , Raeburn Sandy , Dinwoodie Doreen , Wright Alan , May Heather , Calder Kathleen , Barron Lilias , Brock David J. H.
Published: July 2010

An investigation has been made of the social characteristics and knowledge and experience of Huntington disease (HD) for the first 80 individuals considering presymptomatic testing (applicants) at the medical genetics centres in Edinburgh and Glasgow and of attitudes to the test procedure and decisions made after testing for those who received a result. Sixty‐one percent of applicants were female and 31% were over 40 years old. Almost all had a symptomatic parent but 38% did not know HD was in their family until they were over 25 years old and 48% had never received genetic counselling. Thirty‐eight percent of applicants first heard of the test at the genetic clinic, 20% from a relative and 20% from the media, but none had received information from their GP. Thirty‐one applicants did not have the test because they voluntarily withdrew (17 individuals), their family structure was unsuitable or no informative result was possible (11 individuals), or they were diagnosed clinically as being affected (3 individuals). Those who voluntarily withdrew did not differ significantly from the 49 who received a result in social characteristics or knowledge and experience of HD. Twenty‐two individuals were found to be at increased risk (IR) (>50% of becoming affected) and 27 to be at decreased risk (DR) (< 50% of becoming affected). There was a median period of 9 months between entering the test procedure and receiving a result and the main criticism of the procedure was that it took too long to complete and several individuals experienced considerable anxiety while awaiting their result. One year after receiving their result, almost 40% of individuals had made major life decisions, mainly in the areas of personal relationships, career and financial matters and over a third of fecund individuals in both IR and DR groups had changed their decision about future childbearing. Eighty‐five percent of the IR group and 53% of the DR group requested continued follow up after the 1‐year follow‐up visit. The majority wanted follow up by the genetic clinician, but we have found that in practice many individuals do not attend when offered clinic appointments after this time.
Microcephaly with large anterior fontanelle, generalized convulsions, micropenis, and distinct anomalies of the hands and feet. Another example of Wiedemann syndrome?
Authors: Nevin N. C. , Stewart F. J. , Corkey C. W. B. , Bell B. A.
Published: July 2010

Wiedemann et al. (1985) described a rare syndrome characterised by microcephaly, psychomotor delay, short stature, short fingers and toes with stubby broad thumbs and halluces. Unilateral undescended testis, inguinal hernias, scrotal hypoplasia, and micropenis were also features. They described two males, first cousins, whose mothers and maternal grandfather had short broad thumbs and halluces. We report a male with identical features whose parents were normal. This is only the second report of this syndrome. Autosomal or X‐linked dominant inheritance is most likely.
Inv dup(15): contribution to the clinical definition of phenotype
Authors: Grammatico P. , Di Rosa C. , Roccella M. , Falcolini M. , Pelliccia A. , Roccella F. , Del Porto G.
Published: July 2010

One of the primary goals in medical genetics is a precise clinical definition of chromosomal diseases. This is now possible because of the increased number of case reports and new techniques. A male patient, without a clear‐cut syndrome, was cytogenetically investigated. Chromosomal analysis showed a small unidentified bisatellited supernumerary marker. In situ hybridization with a biotin‐labeled DNA probe for the chromosome 15 centromere (D15Z1) demonstrated that the marker was derived from chromosome 15. Hybridization with the Prader‐Willi Syndrome Cosmid biotinylated probe (localized to band 15q11‐q13) showed a signal on both ends suggesting a marker with a symmetrical inv dup(15) and a breakpoint localized in q13. It was then possible to define the karyotype as: 47,XY,+ inv dup(15) (pter‐q13::q13‐pter). All cases of inv dup(15) reported in the literature were reviewed, paying particular attention to the different breakpoints involved, in order to provide a better clinical definition of this syndrome.
Analysis of 40 known cystic fibrosis mutations in South African patients
Authors: Goldman Andrea , Jenkins Trefor , Ramsay Michele
Published: July 2010

A total of 140 South African (SA) Caucasoid cystic fibrosis (CF) families were analysed for the common CF mutation, ΔF508. The 52 non‐ΔF508 CF chromosomes in a subset of 127 of these families were also tested for 39 other known CF mutations. The most frequent mutation, apart from ΔF508 (which occurs at a frequency of 79%), was G542X (1.3%). Four other mutations, R553X, S549N, 621 + 1G→T and N1303K, were each found in single families. The other 35 mutations remained unidentified in this sample of CF families. Since 83% of SA Caucasoid CF mutations have been identified, diagnosis by mutation analysis will be possible in only 69% of CF cases. When a diagnosis has been confirmed by a positive sweat test, a combination of linked marker analysis and mutation detection will be necessary if prenatal diagnosis and carrier detection are to be offered in the remaining families.