bluuebunny/crossref_metadata_2025 huggingface dataset:
Dandy‐Walker malformation and polydactyly: a possible expression of hydrolethalus syndrome
Authors: Morava Eva , Adamovich K. , Czeizel A. E.
Published: July 2010

Hydrolethalus syndrome consists of hydrocephalus, polydactyly, micrognathia, midcranial malformations, visceral abnormalities and perinatal lethality. It was first described in Finland, and only a few other cases outside Scandinavia are known. We report the first Hungarian patient who displayed many signs of the syndrome but had no cleft lip and visceral abnormalities. This observation suggests the existence of oligosymptomic hydrolethalus syndrome, and suggests that Dandy‐Walker malformation with polydactyly may be a manifestation of the hydrolethalus syndrome.
Marker chromosome identification by micro‐FISH
Authors: Engelen John J. M. , Loots Wil J. G. , Motoh Petra C. C. , Moog Ute , Hamers Guus J. H. , Geraedts Joep P. M.
Published: July 2010

Micro‐FISH was used to elucidate the chromosomal origin of marker chromosomes in three patients. Ten copies of marker chromosomes were collected with microneedles from GTG banded metaphases, transferred to a collecting drop and amplified by means of DOP‐PCR. The PCR products were labeled with biotin‐14‐dATP and used as FISH probes for hybridization to normal metaphase chromosomes and to metaphase chromosomes of the patients (reverse painting). With the generation of chromosome region‐specific painting probes by PCR amplification of microdissected DNA and subsequent FISH it was possible to identify the marker chromosomes in all patients. One marker appeared to be derived from the centromere region of the X‐chromosome and the proximal third of the long arm, one from the centromere region of chromosome 17 and one marker chromosome was identified as an isochromosome 18p.
Severe dental aberrations in familial steroid dehydrogenase deficiency: a new association
Authors: Lyngstadaas S. P. , Crossner C‐J. , Nazer H. , Thrane P. S. , Nordbø H.
Published: July 2010

Severe numerical dental aberrations are rare, and are most often seen as a part of certain syndromes. We here report on a Saudi Arabian family where first‐cousin marriages have caused numerical and structural dental abnormalities linked to autosomal recessively inherited liver diseases. The two latest affected children in this family have had their liver defect successfully treated with fat‐soluble vitamins and chenodeoxycholic acid, enabling us to study their dental development. One boy exhibits 11 supernumerary teeth, a general hypomineralisation and enamel hypoplasia, while an affected cousin successfully diagnosed at an early age, so far, only suffers from structural enamel defects. The children are otherwise healthy. There is no resemblance to any known syndromes. We suggest that the supernumerary teeth and the liver disease are caused by the same genetic defect, and represent a new association. The hypomineralisation, however, is most likely to result from vitamin deficiency secondary to malabsorption during the first years of life, before successful treatment was instituted.
Distribution of marker‐Y chromosome containing cells in different tissues of a Turner mosaic patient with mixed gonadal dysgenesis
Authors: Petrusevska R. , Beudt U. , Schäfer D. , Schneider M. , Brude E. , Leitner C. , Heller K. , Arnemann J.
Published: July 2010

We here describe a 12‐year‐old girl with numerous Turner stigmata and virilized external genitalia. Chromosome analysis of PHA stimulated lymphocytes using different banding techniques revealed a 45,X/46,X,+mar Turner mosaicism with the prominent marker present in about 90% of the blood cells. A PCR‐based analysis using a set of 9 STS from different regions of the human Y chromosome indicated the presence of Y chromosomal material with a deletion breakpoint most likely within deletion interval 6. Because of the risk of gonadoblastoma for Turner patients carrying Y chromosomal material, and clinical indications of functional testicular tissue, a gonadectomy in addition to surgical correction of the external genitalia was performed. The histological analysis of the gonads showed a mixture of testicular tissue and ovarian stroma, thus indicating mixed gonadal dysgenesis. Fibroblasts from skin and different parts of the gonads were cytogenetically analyzed and showed a variable distribution of the Y‐derived marker between 4% in skin, 11–31% in gonadal tissue and up to 90% in peripheral lymphocytes.
Four siblings with achalasia, alacrimia and neurological abnormalities in a consanguineous family
Authors: Kasirga Erhun , Özkinay Ferda , Tütüncuoğlu Sarenur , Aydoğdu Sema , Çolakoğlu Zafer , Musoğlu Ahmet , Yağci Ayşe , Taneli Baha , Yağci Raşit V.
Published: July 2010

Four siblings with achalasia, alacrimia and other problems involving the autonomic nervous system involvements are reported. Achalasia and alacrimia were present in all of them. Their parents are first cousins and have four other healthy children. Electrophysiological tests showed that autonomic dysfunction has progressed with age. Blood Cortisol levels were normal in all four affected children. Depending on those findings of our cases and previous reports, we conclude that triple‐A syndrome and achalasia, alacrimia with or without neurological abnormalities could be variable manifestations of the same autosomal recessive gene defect.
Branchio‐oto (BO) syndrome and oculoauriculo‐vertebral phenotype: overlapping clinical findings in a child from a BO family
Authors: Sensi A. , Cocchi G. , Martini A. , Garani G. , Trevisi P. , Calzolari E.
Published: July 2010

A three‐generation BO family is presented: the proband showed, in addition to branchio‐oto malformations, a severe condition with growth retardation, mandibular hypoplasia and vertebral anomalies resembling the oculo‐auriculo‐vertebral (OAV) phenotype. This family study supports the hypothesis of Rollnick and Kaye that the OAV spectrum may represent, in some cases, an extreme component of the BOR syndrome. The finding has relevant implications for genetic counselling regarding both conditions.
A de novo interstitial deletion of chromosome 15 band q25 as revealed by FISH‐technique
Authors: Verma Ram S. , Kleyman Svetlana M. , Giridharan Radha , Ramesh K. H.
Published: July 2010

We report a new chromosomal finding in a 20‐month‐old girl. The minor clinical features included: moderate mental retardation, microcephaly, mild hypotonia and hypertelorism. Initially, what appeared to be a terminal deletion of the long arm of one chromosome 15 [15q26 → qter] was determined to be an interstitial deletion involving band 15q25 as revealed by FISH‐technique, showing the presence of intact telomeric hybridization signals. The cytogenetic diagnosis was thus modified to 46,XX, del (15) (pter → q24::q26 → qter). Nevertheless, the function of the enzyme telomerase should not be ignored, as healing could occur following such terminal deletions. Consequently, it will remain a difficult task to distinguish terminal deletions from those that are interstitial.
Supernumerary ring chromosome 20 characterized by fluorescence in situ hybridization
Authors: van Langen Irene M. , Otter Mariëlle A. , Aronson Daniel C. , Overweg‐Plandsoen W.C.G. , Hennekam Raoul C.M. , Leschot Nico J. , Hoovers Jan M.N.
Published: July 2010

We report on a boy with mild dysmorphic features and developmental delay, in whom karyotyping showed an additional minute ring chromosome in 60% of metaphases. Fluorescence in situ hybridization (FISH) with a centromere specific probe demonstrated that the ring chromosome contained the centromeric region of chromosome 20. The ring was highlighted completely using a chromosome 20 painting probe. A cosmid probe for 20p12‐13 gave a positive signal and hybridization with an all‐telomere probe showed one signal, suggesting a breakpoint in the 20p telomere. The results suggested that only a small part of 20q was involved in this ring. The ring was also detected in 18% of nuclei of a buccal smear. The phenotypic similarities of symptoms in the proband to patients with a (partial) trisomy 20p and the dissimilarities to symptoms in patients with (partial) trisomy 20q were in agreement with the FISH results.
Two novel missense mutations in the LDL receptor gene causing familial hypercholesterolemia
Authors: Gundersen Kaja E. , Solberg Kari , Rødningen Olaug K. , Tonstad Serena , Ose Leiv , Berg Kare , Leren Trond P.
Published: July 2010

We have employed analysis of single‐strand conformation polymorphisms to identify mutations in the low density lipoprotein receptor gene causing familial hypercholesterolemia. Two familial hypercholesterolemia heterozygotes had abnormal single‐strand conformation polymorphism patterns of exons 4 and 8. DNA sequencing revealed that the abnormal pattern of exon 4 was due to heterozygosity (G/T) at nucleotide 502. Nucleotide 502 is the first base of codon 147, and the G→T mutation (D147Y) changes this codon from AspGAC to TyrUAC. The abnormal pattern of exon 8 was due to heterozygosity (A/G) at nucleotide 1097. Nucleotide 1097 is the second base of codon 345, and the A→G mutation (Q345R) changes this codon from GlnCAG to ArgCGG‐ Based upon screening of 437 unrelated familial hypercholesterolemia heterozygotes, both D147Y and Q345R account for about 0.5% of the mutations causing familial hypercholesterolemia in Norway.
Trisomy 18 mosaicism associated with secondary amenorrhea: ratios of mosaicism in different samples and complications
Authors: Uehara S. , Obara Y. , Obara T. , Funato T. , Yaegashi N. , Fukaya T. , Yajima A.
Published: July 2010

A 28‐year‐old woman who complained of irregular menstruation was diagnosed as suffering from trisomy 18 mosaicism. She was karyotyped because of her characteristic face, mild mental retardation and aberrant hyperpigmentation of the skin. Her motor function was within normal range. Physical and laboratory examinations, however, revealed obesity, short stature, minor anomalies of the fingers, many areas of hyperpigmentation on the trunk and the hips, hypergonadotropinemia, diabetes mellitus, liver dysfunction, and hyperlipidemia. The ratios of normal/trisomy 18 were 4:135 in blood lymphocytes, 3:11 in a hyperpigmented area of the skin, 20:0 in a normally pigmented area of the skin, and 14:6 in ascitic cells. Laparoscopy revealed that her ovaries contained neither follicles nor germ cells.
Microcephaly, seizures, genital hypoplasia, and abnormalities of the hands and feet in a 4‐year‐old boy with possible Wiedemann syndrome
Authors: Wieczorek Dagmar , Gillessen‐Kaesbach Gabriele , Plewa Sven , Passarge Eberhard
Published: July 2010

We report on a 4‐year‐old boy with short stature, microcephaly, BNS (Blitz‐Nick‐Salaam) seizures, and global developmental delay. In addition, small and fleshy hands and feet as well as hypoplastic scrotum and testes were observed. The clinical features of the patient are compared with the patients previously described by Wiedemann et al. and Nevin et al. They reported three patients with a syndrome characterized by short stature, microcephaly, global developmental delay, abnormalities of hands and feet, seizures, large anterior fontanelle, scrotal hypoplasia, micropenis, cryptorchism, urinary tract abnormalities, and inguinal hernia (Wiedemann syndrome).
Spectrum of CFTR mutations in Argentine cystic fibrosis patients
Authors: Chertkoff Lilien , Visich Alejandra , Bienvenu Thierry , Grenoville Mario , Segal Edgardo , Carniglia Luis , Kaplan Jean Claude , Barreiro Cristina
Published: July 2010

The identification of different mutations which cause cystic fibrosis (CF) in Argentine patients has been performed. Initially, 10 of the most commonly mutated loci in 228 independent chromosomes were analyzed. Each allele was detected by PCR amplification of DNA samples either directly on polyacrylamide gels, by restriction enzyme digestion and agarose gels electrophoresis, or by hybridization with allele specific oligonucleotides. The AF508 mutation was found in 57% of the alleles. The frequencies of the other CF mutations were as follows: G542X 3.9%, W1282X 3.1%, N1303K 1.7%, 1717 1‐G→A 0.9%, R553X 0.4%, R1162X 0.4%, whereas G551D, AI507 and S549N were not found. This direct mutation analysis enabled the detection of 155/228 CF alleles (67%). Of the remaining 73 unidentified CF alleles, 22 were investigated for the 27 exons by DGGE and 9 rare mutations were identified. The incidence of the main CF mutations analyzed was similar to that of the South European population and markedly different from other Latin American countries. The mutation data presented here may be useful for designing DNA testing strategies for CF in Argentina.
Oculopharyngeal muscular dystrophy (OPMD)‐report and genetic studies of an Australian kindred
Authors: Teh Bin Tean , Sullivan Alice‐Ann , Farnebo Filip , Zander Cecilia , Li Fang Yuan , Strachan Noela , Schalling Martin , Larsson Catharina , Sandstrom Paul
Published: July 2010

Oculopharyngeal muscular dystrophy (OPMD) is a late‐onset autosomal dominant disease. Due to a founder effect, it is most commonly found in the French Canadian population. The gene has recently been mapped to chromosome 14qll.2—q13 in some of these families. Here we report an Australian kindred of German descent with OPMD. Linkage analysis supports its locus to chromosome 14q. Repeat expansion studies were also carried out, but a CAG trinucleotide repeat expansion detected did not cosegregate with the disease. We conclude that there is no evidence of genetic heterogeneity or involvement of repeat expansion in OPMD.
De novo duplication of 7pter→p21.2 and deletion of 9pter→p23.5: clinical and cytogenetic diagnosis
Authors: Back E. , Jung C. , Zeitler S. , Schempp W.
Published: July 2010

We report on a male patient with a de novo derivative chromosome 9. From clinical and conventional cytogenetic data, it was assumed that the derivative chromosome might be caused by a translocation between the short arms of chromosomes 7 and 9: der(9)t(7;9)(p21.2;p23.5). Fluorescence in situ hybridization with a chromosome 7‐specific and a chromosome 9‐specific paint confirmed this supposition. The phenotype of the patient described is compared to cases in the literature.
Chromosome deletion 17pl 1.2 (Smith‐Magenis syndrome) in seven new patients, four of whom had been referred for fragile‐X investigation
Authors: Behjati F. , Mullarkey M. , Bergbaum A. , Berry A. C. , Docherty Z.
Published: July 2010

We report seven new patients with clinical features of the Smith‐Magenis syndrome (SMS) and small de novo interstitial deletions of 17p11.2. Four of these patients had been referred for fragile‐X studies, but standard G‐banded chromosome analysis routinely carried out in addition to the fragility tests revealed the microdeletion in chromosome 17. A relatively high proportion (˜ 2%) of patients referred to this Centre for fragile‐X investigation are found to have a chromosome abnormality other than fra(X) (q27.3), half of them (˜ 1%) with an unbalanced chromosome complement. The four of our seven patients with deletion 17p1 1.2 constitute 25% of those with an unbalanced karyotype, and establish this microdeletion as the most common chromosome abnormality‐except for fra(X) (q27.3)‐in patients referred for fragile‐X screening. The data indicate that standard karyotyping should be offered to patients with this referral indication, in addition to any molecular or chromosome fragility tests for fragile X. We also recommend that the short arm of chromosome 17 be examined critically in these patients. Moderate quality and resolution of banding (450–550 bands per haploid chromosome set) are adequate for detection of the 17p11.2 deletion.
Deletion polymorphism in the angiotensin‐converting enzyme gene is not associated with hypertension in a Gulf Arab population
Authors: Frossard P. M. , Obineche E. N. , Elshahat Y. I. , Lestringant G. G.
Published: July 2010

We have studied an insertion/deletion dimorphism in the human angiotensin‐converting enzyme gene amongst UAE nationals from the Abu Dhabi Emirate. Our findings show lack of association between the I/D allele marker system and clinical diagnosis of essential hypertension, suggesting that variations of the angiotensin‐converting enzyme gene do not play a major role in the determination of elevated blood pressure in this Arab population. This agrees with results reported on other ethnic groups.
Short Communication: Little phenotypic variability in three CF sibs compound heterozygous for the 621 + 1G ← T and the 711 + 1G ← T mutations
Authors: Braekeleer Marc De , Simard Fernand , Aubin Gervais
Published: July 2010

We describe a family in which three sibs are compound heterozygotes for two rather rare CFTR splice‐site mutations, the 621 + 1G → T and the 711 + 1G → T mutations. Little phenotypic variation was observed between sibs, of whom two are deceased. Their disease is characterized by pancreatic insufficiency, a severe pulmonary involvement and major growth retardation.
The atherogenic lipoprotein phenotype is not caused by a mutation in the coding region of the low density lipoprotein receptor gene
Authors: Naggert Jürgen K. , III Adrian Recinos , Lamerdin Jane E. , Krauss Ronald M. , Nishina Patsy M.
Published: July 2010

The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a predominance of small, dense low density lipoprotein particles (subclass pattern B), increased levels of triglyceride‐rich lipoproteins, reductions in high density lipoproteins, and an increased risk for myocardial infarction. In a previous linkage study of 11 families, evidence for tight linkage of subclass pattern B with the LDL receptor (LDLR) locus on chromosome 19p13.2 was obtained. To test whether a mutation in the structural portion of the LDLR gene could be responsible for the phenotype, we first sequenced the exons of the receptor binding domain for each pair of parents in these 11 pedigrees. For the remaining portion of the LDLR coding region, exons as well as cloned LDLR cDNAs were sequenced for selected members of the pedigrees. No mutations that changed the amino acid sequence of the LDLR were found. We conclude that it is unlikely that a mutant allele of the LDLR protein is responsible for ALP.
Case Report: Corroboration of the lower extremity counterpart of the Poland sequence
Authors: Corona‐Rivera J. Román , Corona‐Rivera Alfredo , Totsuka‐Sutto Sylvia E. , Corona‐Rivera Enrique
Published: July 2010

Gluteal and lower extremity hypoplasia with ipsilateral toe brachysyndactyly were noted in a 23‐year‐old woman similarly affected to the only previously reported case of the lower extremity counterpart of Poland sequence. Since no neurological deficit was found, and electromyographic and nerve conduction studies in the affected limb were normal, we propose a vascular origin which would involve the external iliac artery supply analogous to the subclavian artery supply disruption in the upper extremity Poland sequence.
Prenatal detection of double aneuploidy trisomy 10/monosomy X in a liveborn twin with exclusively monosomy X in blood
Authors: Mielke G. , Enders H. , Goelz R. , Klein‐Vogler U. , Ulmer R. , Trautmann U.
Published: July 2010

Both double aneuploidy and trisomy 10 are rare chromosome findings. All five published cases of trisomy 10 in liveborns were found to be mosaic with an euploid cell line. In a liveborn female twin, double aneuploidy mosaicism 47,XX, + 10/45,X was detected prenatally by amniocentesis performed because of severe intrauterine growth retardation and malformations. Chromosome analysis from neonatal lymphocyte cultures revealed exclusively the 45,X cell line. Double aneuploidy mosaicism trisomy 10/monosomy X was confirmed from skin fibroblasts. The child died at the age of 7 weeks. This is the first reported case of double aneuploidy involving trisomy 10, and the first case of trisomy 10 without a normal cell line in a liveborn. Prenatal diagnosis of trisomy 10 in a liveborn has not been published so far. The case illustrates that in specific cases amniotic fluid cells may reflect the karyotype of the fetus better than blood.
Complex chromosome rearrangement involving chromosomes 1, 4 and 16 revealed by fluorescence in situ hybridization
Authors: Johannesson T. , Ehlers S. , Wahlström J.
Published: July 2010

A 7‐year‐old boy with mental retardation had apparently balanced reciprocal translocations, involving the telomeric regions of chromosomes 1p and 4q, which was detected by routine chromosome analysis. Fluorescence in situ hybridization (FISH) was used and also revealed the telomeric region of chromosome 16p to be involved in a still apparently balanced translocation‐complex, impossible to discover with classical cytogenetic analysis. We want to emphasize the importance of FISH in detecting small chromosomal aberrations. We discuss whether the abnormal phenotype is caused by unbalanced karyotype with cryptic undetected translocations or small deletions or mutations in the translocation‐breakpoints.
High prevalence of a novel mutation in the exon 4 of the low‐density lipoprotein receptor gene causing familial hypercholesterolemia in Belgium
Authors: Descamps O. , Hondekijn J‐C. , Acker P. Van , Deslypere J‐P. , Heller F. R.
Published: July 2010

In a cohort of 70 unrelated patients living in Southern Belgium with autosomal dominantly inherited hypercholesterolemia, 11 had a hitherto undescribed mutation in exon 4. It consisted inaC→A mutation at nucleotide 366, resulting in a stop codon at residue Cys122. This C122X mutation is expected to cause a class I receptor defect. The biochemical and clinical data collected from the patients carrying the mutation were consistent with a severe form of familial hypercholesterolemia (FH). Some differences between generations were noted. Amongst the C122X carriers, those born after 1926 had cardiovascular complications earlier than those born before 1926. This raises the possibility that changes in environmental factors during the course of the century have had an unfavorable impact on the prognosis of the disease. The mutation was found in 16% of the suspected FH patients and less frequently (less than 3% of suspected FH) in Northern Belgium. The haplotype of the chromosomes carrying the mutation was the same in all C122X families, but extensive genealogical studies failed to reveal a common ancestor. We conclude that C122X is an old and common cause of FH in Belgium. Screening for this mutation may be useful in the diagnosis of FH in Belgium.
Two novel missense mutations in the ATP‐binding domain of the adrenoleukodystrophy gene: immunoblotting and immunocytological study of two patients
Authors: Imamura Atsushi , Suzuki Yasuyuki , Song Xiang‐Qian , Fukao Toshiyuki , Uchiyama Atsushi , Shimozawa Nobuyuki , Kamijo Keiju , Hashimoto Takashi , Orii Tadao , Kondo Naomi
Published: July 2010

Two novel missense mutations, 1939G to A (R518Q) and 20I7A to G (Q544R) were identified in Japanese patients with adrenoleukodystrophy (ALD). They are located in exon 6, which encodes part of the putative adenosine triphosphate binding domain of ALD protein. The ALD protein carrying the R518Q mutation was undetectable in fibroblasts, by immunoblot and immunofluorescence analysis, white the Q544R mutation had no apparent effect on the stability and localization of the ALD protein, but is expected to affect its function.
Lissencephaly associated with cerebellar hypoplasia and myoclonic epilepsy in a Bedouin kindred: a new syndrome?
Authors: Farah S. , Sabry M. A. , Khuraibet A. , Khaffagi S. , Rudwan M. , Hassan M. , Haseeb N. , Abulhassan S. , Abdel‐Rasool M. A. , Elgamal S. , Qasrawi B. , Al‐Busairi W. , Farag T. I.
Published: July 2010

Clinico‐radiological assessment of three mentally retarded members of a large Bedouin kindred showed lissencephaly, spastic paraparesis, myoclonic epilepsy and cerebellar hypoplasia. It seems that the familial association of lissencephaly/myoclonic epilepsy/cerebellar hypoplasia represents a new entity.
CpG hotspot mutations at the LDL receptor locus are a frequent cause of familial hypercholesterolemia among South African Indians
Authors: Kotze Maritha J. , Loubser Odell , Thiart Rochelle , de Villiers J. Nico P. , Langenhoven Elzet , Theart Leonora , Steyn Krisela , Marais A. David , Raal Frederick J.
Published: July 2010

Mutation analysis of genomic DNA samples obtained from seven unrelated South African Indians with familial hypercholesterolaemia (FH) revealed two novel and two recurrent missense mutations in the low density lipoprotein receptor (LDLR) gene. The novel mutations are transversions of C to G and A to T at nucleotide positions 1215 (N384K) and 2356 (S765C), respectively. The known mutations were detected in CpG dinucleotides at bases 661 and 682, respectively, in the mutation‐rich exon 4 of the LDLR gene. Mutation D200Y was found in a single FH family, while mutation E207K was detected in two apparently unrelated Indian families on a new mutual haplotype. Analysis of published mutations including our new data has shown that more than 50% of the different LDLR gene mutations identified to date in South African Indians occur at CpG hotspots.
Geographic distribution of French‐Canadian low‐density lipoprotein receptor gene mutations in the Province of Quebec
Authors: Vohl Marie‐Claude , Moorjan Sital , Roy Madeleine , Gaudet Daniel , Torres Ana Lucia , Minnich Ann , Gagné Claude , Tremblay Gérald , Lambert Marie , Bergeron Jean , Couture Patrick , Perron Patrice , Blaichman Shirley , Brun Louis‐Daniel , Davignon Jean , Lupien Paul J. , Després Jean‐Pierre
Published: July 2010

A total of 35 homozygous and 1320 heterozygous patients with familial hypercholesterolemia (FH) was screened for the presence of six low‐density lipoprotein receptor (LDLR) gene mutations previously reported among French‐Canadians. The geographic distribution of patients' birthplaces and the relative prevalence of these six mutations in the LDLR gene in the province of Quebec were compared. For this purpose, the 16 administrative regions of the province of Quebec were grouped into seven geographic regions. The relative frequency of the six mutations differed in the seven regions: the > 15 kb deletion (& Delta; >15 kb) had the highest relative frequency in the Bas St‐Laurent/Gaspésie region, and the point mutation in exon 3 had the highest relative frequency in the Saguenay‐Lac‐St‐Jean/Cǒte‐Nord region. In the Montreal area, the Δ >15 kb and the mutation in exon 3 had prevalence rates of 71.2% and 13.0%, respectively, whereas the relative frequencies of the Δ > 15 kb and the point mutation in exon 3 in the Quebec city region were 57.5 and 21.8%, respectively. Finally, in Saguenay‐Lac‐St‐Jean/Cǒte‐Nord, the relative frequency of the Δ > 15 kb only reached 31.5% and the point mutation in exon 3, 59.2%. Thus, on the north shore of the St. Lawrence River, the prevalence of the Δ > 15 kb decreases from west to north‐east, whereas the relative frequency of the mutation in exon 3 appears to increase. These observations provide a better characterization of FH among French‐Canadians of Quebec, a Canadian province with a high prevalence of this inherited disease.
Incomplete penetrance and expressivity skewing in hereditary multiple exostoses
Authors: Legeai‐Mallet Laurence , Munnich Arnold , Maroteaux Pierre , Merrer Martine Le
Published: July 2010

Hereditary multiple exostosis (EXT) is an autosomal dominant skeletal disorder characterized by the formation of cartilage‐capped prominences developing from the juxta‐epiphyseal regions of the long bones and causing orthopedic deformities and occasionally sarcomatous degeneration. Reviewing a large cohort of 175 EXT patients referred to us over the last 40 years (1955–1995), we found 109 familial forms (62%) and 66 isolated cases (38%). The disease is consistently diagnosed before the age of 12 years and the risk of malignancy, although increased, is quite modest in our series (0.57%). The observation of seven unaffected individuals (six females, one male) with a family history and affected offspring supports the incomplete penetrance of the disease. Moreover, the observation of an unequal sex‐ratio with a preponderance of males among probands in this series (103: 72, p < 0.02) and in all series reported to date (198: 133, p < 0.001) gives support to the variable penetrance of EXT genes among sexes. Whether this incomplete penetrance is associated with one of the disease genes recently identified in EXT is currently under investigation.
A new multiple malformation syndrome of Müllerian dysgenesis and conductive hearing loss with facial hypoplasia, bilateral forearm deformity, brachydactyly, spinal stenosis and scoliosis
Authors: Kumar D. , Masel J. P.
Published: July 2010

Multiple congenital malformations in a young girl with bilateral conductive hearing loss are described. Facial dysmorphic features include prominent supraorbital ridges, facial hypoplasia, facial asymmetry, downward‐slanting palpebral fissures, high prominent nasal bridge with bifid nasal tip and a small lower jaw, and hypoplastic ear lobules with bilaterally narrow and oblique external auditory canals. Recognisable skeletal abnormalities include hypoplastic facial bones, hypoplastic clavicles, narrow and anteriorly sloping shoulders, bowing of both forearm bones, brachydactyly due to short metacarpals and hypoplastic terminal phalanges, thoracolumbar kyphoscoliosis, narrow transverse measurements of most vertebrae with prominent coccyx, spinal canal narrowing, hypoplasia of lower ilia, medially bowed femora, tibiae and fibulae and brachysyndactyly of the second, third and fourth toes bilaterally. Gynaecological evaluation revealed abnormalities of the Müllerian duct structures: urogenital sinus, a vestigial uterus, a posteriorly placed small but patent vagina and a septum at the vaginal introitus. The pattern of MCA probably refers to a new syndrome within the “community of syndromes” involving anomalies of the Müllerian duct structures, limbs, spine and external ears.
Benign familial microcytic thrombocytosis with autosomal dominant transmission
Authors: Cohen Natan , Almoznino‐Sarafian Dorit , Weissgarten Joshua , Alon Irena , Zaidenstein Ronit , Dishi Victor , Rahimi‐Levene Naomi , Fried Kalman , Modai David , Golik Ahuva
Published: July 2010

Familial thrombocytosis is an extremely rare disorder, so far reported in only a handful of families. In the majority of cases the characteristics were of essential thrombocythemia. Most patients presented with a platelet count above 800000/mm3, were diagnosed as having a myeloproliferative disease, and some required chemotherapy. We describe a benign form of familial thrombocytosis with autosomal dominant inheritance in five healthy members of three generations of a family, all of whom had moderate thrombocytosis within the range 422 000–662 000/mm3, characterized by low mean platelet volume. A careful medical history and a 5‐year follow up of the subjects did not reveal any untoward clinical development. This variant of familial thrombocytosis is therefore of a benign nature. Possible mechanisms linking thrombocytosis with platelet microcytosis in this family are discussed.
Essential hyperhidrosis in Turner syndrome
Authors: Noppen M. , Vincken W.
Published: July 2010

We describe two Turner patients suffering from severe essential hyperhidrosis. Since both disorders are rare (1 in 5000 live female births for Turner syndrome and approximately 1 in 1000 persons for essential hyperhidrosis), our finding of two patients with these disorders in a total of 150 essential hyperhidrosis patients may suggest that this association is more frequent in Turner syndrome than previously thought.
China's genetic services providers' attitudes towards several ethical issues: a cross‐cultural survey
Authors: Mao Xin , Wertz Dorothy C.
Published: July 2010

Attitudes towards ethical, legal and social issues in genetic research and practice were investigated in 402 genetic services providers from 30 provinces and autonomous regions in China. This was done using a Chinese version of an international survey questionnaire on ethics and genetics that has been circulated in 37 nations. In all, 255 study participants completed questionnaires (63%). The majority of the respondents (89%) reported that they agreed with the current Chinese laws and regulations on termination of pregnancy for genetic abnormalities and non‐medical indications, on the basis of considerations of population control and family planning. More than half the respondents opposed sex selection by prenatal diagnosis in the absence of an X‐linked disorder. However, most of them (86%) would prefer directive counseling. More than half would agree to disclose genetic information to relatives at risk, and would permit third parties such as law enforcement agencies, spouse/partner, blood relatives, employers involving public safety, life and health insurers to access stored DNA without consent. The majority (73%‐98%) also thought that DNA fingerprinting should be required for prisoners convicted of or charged with crimes, members of armed forces and all newborns. Although these are only the first part of the results of our international survey, they provide an initial basis for international discussion on ethics and genetics in China.
GAPO syndrome: first Egyptian case with ultrastructural changes in the gingiva
Authors: Meguid Nagwa A. , Afifi Hanan H. , Ramzy Magda I. , Hindawy Amina , Temtamy Samia A.
Published: July 2010

We report on a 3‐year‐old boy with growth retardation, alopecia, pseudoanodontia, and optic atrophy. This is the 18th known and the first Egyptian case of GAPO syndrome. Electron microscopic examination of gingival biopsy showed excessive collagen fibres and endothelial vacuolisation, suggesting involvement of extracellular pathological collagenosis.
Mild phenotypic manifestations of terminal deletion of the long arm of chromosome 4: clinical description of a new patient
Authors: Caliebe A. , Waltz S. , Jenderny J.
Published: July 2010

We present clinical and developmental data on a patient with a de novo terminal deletion of the long arm of chromosome 4. Cytogenetic studies after G‐banding revealed the karyotype 46,XY,del(4)(q34). The 4‐year‐old male showed mild facial dysmorphism, moderate mental retardation with speech retardation, and marked deficits in gross motor skills. Our patient is the second with this deletion described in the literature. In both patients the phenotype was characterized by mild to moderate mental retardation, abnormalities of the pinnae, and nonspecific facial dysmorphism. The mild phenotype might explain why only two patients with this deletion have been described so far.
Expand Long PCR for fragile X mutation detection
Authors: Hećimović Silva , Barišić Ingeborg , Müller Andreas , Petković Iskra , Barić Ivo , Ligutić Ivo , Pavelić Krešimir
Published: July 2010

Fragile X mutation detection by DNA analysis enables accurate diagnosis of the fragile X syndrome. The mutation involves the expansion of CGG repeats in the FMR1 gene and has been primarily detected by the Southern blotting method. In this study we present a novel, efficient and reliable PCR protocol that is more convenient for routine diagnosis of the fragile X syndrome. This method is based on the use of the Expand Long PCR System, which enables the amplification of normal, premutated and full‐mutated alleles, and therefore provides complete CGG repeat analysis of the FMR1 gene. Normal alleles were easily detected by ethidium bromide staining of the agarose gels, suggesting that this assay could be used as a screening test for a large number of referrals. The amplified premutations and full mutations were identified by hybridization with a digoxigenin‐labeled 5′‐(CGG)5–3′ probe, followed by chemiluminescent detection. The accuracy of our Expand Long PCR protocol was confirmed by Southern blot analysis, illustrating that the Expand Long PCR results concur with those of Southern blotting. In this paper we propose a new strategy for molecular diagnosis of the fragile X syndrome in which our Expand Long PCR assay is used as the first screening test for fragile X mutation detection.
Differences in the prevalence of a TaqI RFLP in the 3‘ flanking region of the α1‐proteinase inhibitor gene between asthmatic and non‐asthmatic black and white South Africans
Authors: Green Samantha L. , Gaillard M. Christine , Dewar John B. , Ludewick Herbert , Song Ernest , Feldman Charles
Published: July 2010

The prevalence of the Taq I(‐) allele in variants of α1‐proteinase inhibitor (α1PI) was investigated in a group of 28 black asthmatic patients and 32 black control individuals, and was compared to 43 white asthmatic patients and 32 white control individuals. The plasma concentration of α1PI was determined in eight black and 14 white asthmatics without the Taq I(‐) allele, and compared to seven black and three white asthmatics with the Taq I(‐) allele. Alpha‐1‐PI concentration was also determined in 10 black and 29 white control individuals without the Taq I(‐) allele and compared to seven black and three white controls with the Taq I(‐) allele. There was a highly significant difference in the frequency of the Taq I(‐) allele between black South Africans (24.1%) and white South Africans (6%) (p<0.00001) and a significant difference in the frequency of the Taq I(‐) allele between black asthmatics and white asthmatics (p = 0.0004) and between black controls and white controls (p = 0.011). The Taq I(‐) allele was significantly associated with the Ml(Val213) variant as compared to the Ml (Ala213) of α1PI (p = 0.0042). There was no difference in the concentration of α1PI between the asthmatics (black and white) lacking the Taq I(‐) allele and the asthmatics (black and white) with the allele. However, a significant increase in plasma α1PI concentration was found in the asthmatics compared to the controls (p = 0.011). The Taq I(‐) allele did not seem to interfere with the basal expression of α1PI in the groups of asthmatic patients in this study.
Influence of APOH protein polymorphism on apoH levels in normal and diabetic subjects
Authors: Ruiu Gianluca , Gambino Roberto , Veglia Fabrizio , Pagano Gianfranco , Cassader Maurizio
Published: July 2010

Apolipoprotein (apo)H (also known as β2 glycoprotein‐I) is a glycoprotein synthesized by liver cells and it is present in the blood associated with plasma lipoproteins. APOH displays a genetically determined structural polymorphism: three alleles (APOH*1, APOH*2, APOH*3) at a single locus on chromosome 17 code for different isoforms, and population studies have shown that APOH*2 is the most frequent allele. This paper assesses the relation between APOH phenotypes and plasma apoH levels in a population composed of 278 healthy subjects (243 H2/2, 32 H3/2, 2 H3/3, 1 H2/1; allele frequencies APOH*1 0.002, APOH*2 0.934, APOH*3 0.064) and 245 diabetics (212 H2/2, 30 H3/2, 3 H3/3; allele frequencies APOH*2 0.927 and APOH*3 0.073). Determination of apoH levels by competitive ELISA gave a mean value of 26.3 ± 9.8 mg/dl for all subjects, 22.6 ± 7.7 in normals vs 30.6 ± 10.3 in diabetics (p = 0.0001), and 23.0 ± 7.9, 19.3 ± 5.4 and 18.5 ± 3.5 mg/dl for H2/2, H3/2 and H3/3 in normals and 31.1 ± 10.1, 28.2 ± 10.8 and 15.7 ± 9.0 mg/dl in diabetics, respectively. ANCOVA of the adjusted data revealed a significant difference in apoH levels for the three phenotypes in both the normal subjects (p = 0.01) and the diabetics (p = 0.02). ANCOVA of the whole samples of subjects, controlling for diabetes as well as age, sex and total cholesterol, indicated a substantial effect of phenotype, independent of the other variables (p = 0.0007).
A case of de novo interstitial deletion of chromosome 5(q33q34)
Authors: Giltay Jacques C. , Gerssen‐Schoorl Klasien B. J. , Luitse Gert H. J. , Dauwerse Hans G.
Published: July 2010

The present paper describes a girl with a small de novo deletion of chromosome 5(q33q34). Fluorescence in situ hybridisation with locus specific probes was used to define the extent of this deletion. Clinical features in this patient are microcephaly, dysmorphic facial features such as epicanthus, small biparietal distance and retrognathia, four‐finger lines on both hands and mild mental retardation.
An additional case of craniodigital syndrome: variable expression of the Filippi syndrome?
Authors: Orrico A. , Hayek G.
Published: July 2010

We report on a boy with severe growth and mental retardation, syndactyly of toes and facial anomalies. This phenotype can easily be classified in the group of craniodigital syndromes, but it is difficult to make a more clearly defined diagnosis, based on other minor anomalies, because of the presence of overlapping features. On the basis of various pathognomic features, we conclude that our patient could be an additional case of Filippi syndrome. Moreover, newly recognised features in this patient may be due to variability in phenotypic expression.
Rhombencephalosynapsis with facial anomalies and probable autosomal recessive inheritance: a case report
Authors: Romanengo Marta , Tortori‐Donati Paolo , Rocco Maja Di
Published: July 2010

We report a 16‐year‐old boy, born to consanguineous parents, with mental retardation, gait disturbances and dysarthria; brain magnetic resonance showed features consistent with rhombencephalosynapsis. This condition is characterised by a hypoplastic single‐lobed cerebellum. The interest of this case is the presence of common ancestors, pointing to an autosomal recessive inheritance of the malformation.
Turner syndrome in a mother and daughter: r(X) and fertility
Authors: Blumenthal Andrea L. , Allanson Judith E.
Published: July 2010

A patient with mosaic Turner syndrome and normal fertility had three documented pregnancies. She had a 45,X/46,X,r(X) karyotype and did not undergo spontaneous sexual maturation and menarche. Conception occurred while on hormone replacement therapy. Her first pregnancy ended with the birth of a normal 46,XY male, while the third pregnancy resulted in a healthy 45,X/46,X,r(X) female. A review of the literature reveals a myriad of theories to account for the variability of ovarian function in Turner syndrome, but, as yet, there are insufficient data to yield any conclusions. There appears to be an increased risk of trisomy 21 in the offspring of females with Turner syndrome.
Osteopathia striata with cranial sclerosis: highly variable phenotypic expression within a family
Authors: Savarirayan Ravi , Nance Jane , Morris Lloyd , Haan Eric , Couper Richard
Published: July 2010

We report a four‐generation family, with five individuals affected by osteopathia striata with cranial sclerosis (OS‐CS). The family illustrates the wide spectrum of gene expression in this autosomal dominant condition. Of particular note is the unusually severe expression in the proband, who exhibits virtually all of the reported associations of the syndrome. Proximal osteolysis of the fibula and congenital urological abnormalities, in the proband, and holoprosencephaly sequence, in the proband's sister, have not previously been described in the syndrome.
Scalp defect, absence of nipples, ear anomalies, renal hypoplasia: another case of Finlay‐Marks syndrome
Authors: Plessis G. , Treust M. Le , Merrer M. Le
Published: July 2010

The association of scalp defect, unusual ears and absence of nipples was described by Finlay & Marks as an autosomal dominant trait. We report a new case in a 23‐year‐old woman. Renal insufficiency and cataract seem to be frequent and must be investigated.
Cardiovascular risk factors in people with different genotypes in the insertion/deletion (I/D) polymorphism at the locus for angiotensin I‐converting enzyme (ACE)
Authors: Berge K. E. , Berg K.
Published: July 2010

The deletion (D) allele of an insertion/deletion (I/D) polymorphism at the locus for angiotensin I‐converting enzyme (ACE) has been reported to be an independent risk factor for myocardial infarction (MI), particularly in people lacking traditional risk factors. Furthermore, a borderline association between Lp(a) lipoprotein level and the I/D polymorphism at the ACE locus was reported in one study. We have searched for possible “level gene” or “variability gene” effects of ACE genes on Lp(a) lipoprotein, total cholesterol (TC), high density lipoprotein (HDL) cholesterol (HDLC), low density lipoprotein (LDL) cholesterol (LDLC), triglycerides (TG), apolipoprotein B (apoB), apolipoprotein A‐I (apoA‐I), and body mass index (BMI). None of these variables differed significantly between genotypes in the I/D polymorphism in any of three population samples. A single population sample created by combining the three series, exhibited an insignificant trend towards individuals carrying the D‐allele having a higher level of Lp(a) lipoprotein than those lacking it, and DD homozygotes had a significantly higher Lp(a) lipoprotein level than the combined group of ID/II individuals (p = 0.03). These results may indicate that the D‐allele of the I/D polymorphism at the ACE locus could influence the level of Lp(a) lipoprotein.
Case Report: Partial trisomy of 15q due to inserted inverted duplication
Authors: Elçioglu Nursel , Fear Claudine , Berry A. Caroline
Published: July 2010

Ade novoabnormal chromosome 15, with an inverted duplication of the segment (15q13.3 → 15q21.3) at 15q24.3, was found in a boy with mild developmental delay, facial dysmorphism, Marfan‐like appearance and severe language delay. There is an unusual disparity between the severe lack of speech and the presence of reasonable skills in other areas.
Apolipoprotein(a) is a human vascular endothelial cell agonist: studies on the induction in endothelial cells of monocyte chemotactic factor activity
Authors: Poon Michael , Zhang Xiaoxia , Dunsky Kevin , Taubman Mark B. , Harpel Peter C.
Published: July 2010

Elevated levels of lipoprotein(a), Lp(a), are associated with premature atherosclerosis; however, the mechanisms of its atherogenicity are not known. Recruitment of monocytes to the blood vessel wall is an early event in atherogenesis. Since Lp(a) is associated with macrophages in the plaque, we have examined the effect of Lp(a) on inducing monocyte chemotactic activity (MCA) in vascular endothelial cells. We report that Lp(a) and apo(a) induced human umbilical vein (HUVEC) and coronary artery endothelial cells to secrete monocyte chemotactic activity as early as 30 min of incubation. In the absence of cells, Lp(a) had no direct monocyte chemotactic activity. Actinomycin D and cycloheximide inhibited the HUVEC response, indicating that protein and RNA synthesis were required. Endotoxin was shown not to be responsible for the induction of monocyte chemotactic activity. Granulocyte monocyte‐colony stimulating factor antigen was not detected in the Lp(a)‐conditioned medium, nor was monocyte chemoattractant protein‐1 mRNA induced by Lp(a). These results suggest that Lp(a) may be involved in the recruitment of monocytes to the vessel wall, thus providing a novel mechanism for the participation of Lp(a) in the atherogenic process.
Biogenesis of Lp(a) in transgenic mouse hepatocytes
Authors: White Ann L.
Published: July 2010

Lipoprotein(a) [Lp(a)] biogenesis was examined in primary cultures of hepatocytes isolated from mice transgenic for both human apolipoprotein(a) [apo(a)] and human apoB. Steady‐state and pulse‐chase labeling experiments demonstrated that newly synthesized human apo(a) had a prolonged residence time (˜60 min) in the endoplasmic reticulum (ER) before maturation and secretion. Apo(a) was inefficiently secreted by the hepatocytes and a large portion of the protein was retained and degraded intracellularly. Apo(a) exhibited a prolonged and complex folding pathway in the ER, which included incorporation of apo(a) into high molecular weight, disulfide‐linked aggregates. These folding characteristics could account for long ER residence time and inefficient secretion of apo(a). Mature apo(a) bound via its kringle domains to the hepatocyte cell surface before appearing in the culture medium. Apo(a) could be released from the cell surface by apoB‐containing lipoproteins. These studies are consistent with a model in which the efficiency of posttranslational processing of apo(a) strongly influences human plasma Lp(a) levels, and suggest that cell surface assembly may be one pathway of human Lpfa) production in vivo. Transgenic mouse hepatocytes thus provide a valuable model system with which to study factors regulating human Lp(a) biogenesis.