bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstitial deletion of 8p: report of two patients and review of the literature
Authors: Tsukahara Masato , Murano Ichiro , Aoki Yoshiharu , Kajii Tadashi , Furukawa Susumu
Published: July 2010

Two female infants with de novo interstitial deletions of 8p were studied. One with a deletion from p11.21 to p11.23, and the other patient with a deletion from p11.23 to p21.3 had several clinical manifestations of the terminal 8p— syndrome. Band 8p11.23 was deleted in both patients. The clinical manifestations common to both patients included low birth‐weight, growth deficiency, congenital heart disease, mental retardation, dolichocephaly, low‐set, malformed ears, high‐arched palate, thin lips and micrognathia. Since these features may occur in most patients with chromosomal imbalance, and the terminal 8p— syndrome has hitherto been assumed to result from terminal deletions of 8p, ranging from p21.3 to p23, it is likely that these features are simply related to the chromosomal imbalance rather than to band specific imbalance of 8p11.23. The present study suggests that two different types of deletion, interstitial and terminal, are associated with still poorly defined, rather non‐specific clinical features.
Identification of a CD40L gene mutation and genetic counselling in a family with immunodeficiency with hyperimmunoglobulinemia M
Authors: Kraakman Margriet E. M. , de Weers Michel , Español Teresa , Schuurman Ruud K. B. , Hendriks Rudolf W.
Published: July 2010

A 13‐year‐old boy with immunodeficiency with hyper‐IgM was analyzed for mutations in the CD40L gene. An insertional mutation of an extra T in a run of four T's was found in the second exon of the gene, leading to a premature translation stop. Genetic counselling of the family was performed, based on mutation detection by PCR/oligohybridization.
Vitamin D dependent rickets type II and normal vitamin D receptor cDNA sequence. A cluster in a rural area of Cauca, Colombia, with more than 200 affected children
Authors: Giraldo A. , Pino W. , García‐Ramírez L. F. , Pineda M. , Iglesias A.
Published: July 2010

Vitamin D dependent rickets type II is an autosomal recessive disease caused by the vitamin D defective receptor. More than 200 patients with different types of lower limb deformities were detected in a rural area of the Cauca department in the southwest part of Colombia. Patients were well nourished and in good physical condition in spite of their deformities. None of them presented alopecia, myopathy, seizures or aminoaciduria. Serum analysis showed significantly lower serum calcium as compared to normal relatives, though in the normal low range, normal phosphorus, high alkaline phosphatase, normal 25‐hydroxyvitamin D3 and high 1,25‐dihydroxyvitamin D3, indicating target organ resistance. The cDNA analysis showed normal nucleotide sequence. We suggest that our patients represent a distinct form of receptor‐positive resistance to vitamin D. This report is the first extensive study on this class of patients.
Lack of association of apolipoprotein E polymorphism with plasma Lp(a) levels in the Chinese
Authors: Heng C. K. , Saha N. , Tay J. S. H.
Published: July 2010

Apolipoprotein E (apoE) polymorphism and its influence on plasma lipids, lipoproteins, lipoprotein (a) [Lp(a)] and apolipoproteins was studied in 536 (270 males and 266 females) healthy Chinese in Singapore. From analysis of variance with age and BMI as covariates, apoE genotype was found to exert a significant influence on plasma total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) and apoB in females. Its effect in males was marginally significant only on LDL‐C. In both sexes, plasma TC, LDL‐C and apoB were lower in those who were E2‐3 than in those who were E3‐3. There was no significant difference in log‐transformed Lp(a) level between the apoE genotypes after adjusting for the confounding effect of LDL‐C in addition to age and BMI. The percentage variance (R2times100) of the lipid traits explained by apoE polymorphism in the females was 4.94% for plasma TC, 5.85% for LDL‐C and 4.25% for apoB. We conclude that: 1) ε2 allele had a lowering effect on plasma TC, LDL‐C and apoB; 2) apoE polymorphism did not have any significant influence on Lp(a) concentration; and 3) the effect of apoE polymorphism on plasma TC, LDL‐C and apoB was gender‐specific, with a stronger influence in females than in males.
Retinitis pigmentosa in Spain
Authors: Ayuso C. , Garcia‐Sandoval B. , Najera C. , Valverde D. , Carballo M. , Antiñolo G. ,   Spanish Multicentric and Multidisciplinary Group for Research into Retinitis Pigmentosa
Published: July 2010

Retinitis pigmentosa is a term commonly given to a group of inherited and progressive disorders which affect the photoreceptors of the retina. As part of an ongoing research programme throughout Spain, clinical, epide‐miological, and genetic studies have been carried out on these diseases. Here, we report the relative frequencies of the different genetic types in 503 non‐syndromic and 89 syndromic RP families of Spanish origin. The most frequent syndromic RP forms were Usher syndrome type 1 (20/ 89 families=30%) and Usher syndrome type 2 (44 families=49%). Among non‐syndromic RP forms, 12% were autosomal dominant, 39% autosomal recessive and 4% X‐linked. Forty‐one percent were isolated or simplex cases and in 4% the genetic type could not be established.
On the nosology of the “primary true microcephaly, chorioretinal dysplasia, lymphoedema” association
Authors: Fryns Jean‐Pierre , Smeets Eric , Van den Berghe H.
Published: July 2010

We describe a male child with prenatal growth retardation, true microcephaly, pedal lymphoedema and characteristic ocular anomalies. Ophthalmological examination revealed remnants of the posterior hyaloidea, more pronounced in the right eye where a retinal fold extended from the papilla into the vitreum, chorioretinal dysplasia with narrow retinal vessels, multiple large round areas of chorioretinal atroph and atrophic papillae. The associations “Microcephaly‐chorioretinal dysplasia”, “Microcephaly‐retinal folds” and “Microcephaly‐lymphoedema” have been reported as separate autosomal dominant conditions. The findings in the present child suggest that these associations could be variable expressions of the same autosomal dominant condition.
Molecular cytogenetic studies of duplication 9q32→q34.3 inserted into 9q13
Authors: Hou Jia‐Woei , Wang Tso‐Ren
Published: July 2010

Fluorescence in situ hybridization (FISH) studies using whole chromosome 9 painting probe, classical satellite (9q12‐specific) probe and abl cosmid probe (locus: 9q34) were performed on a female infant who was born with multiple congenital anomalies and the karyotype 46,XX, 9q+. The results of FISH confirm the euchromatic nature of the extra material on the long arm of chromosome 9, and provide evidence that it is of chromosome 9 origin. The structural rearrangement has probably resulted from an insertion of a duplicated segment 9q32→q34.3 into band q13, as shown by the abl cosmid probe. The clinical features in this patient are similar to the previously reported cases of partial trisomy 9q3.
Spondylo‐camptodactyly syndrome: a distinct autosomal dominant entity?
Authors: Lizcano‐Gil L. A. , García‐Cruz D. , Sánchez‐Corona J. , Cantü J. M.
Published: July 2010

We present a family in which five members over three generations have a syndrome characterized by camptodactyly, flattened bodies of cervical vertebrae, and a variable degree of thoracic scoliosis. After excluding other camptodactyly syndromes, it was concluded that this association of anomalies probably represents a new autosomal dominant syndrome.
Polysyndactyly and asymptomatic hypothalamic hamartoma in mother and son: a variant of Pallister‐Hall syndrome
Authors: Löw M. , Moringlane J. R. , Reif J. , Barbier D. , Beige G. , Kolles H. , Kujat C. , Zang K. D. , Henn W.
Published: July 2010

We report on a 53‐year‐old woman and her 20‐year‐old son who both presented with polysyndactyly, without other external malformations or mental retardation. MRI imaging revealed, as an incidental finding, asymptomatic hypothalamic hamartomas in both patients. The siblings of both mother and son are unaffected. This family may represent an autosomal dominant variant of Pallister‐Hall syndrome.
Osteopenia, abnormal dentition, hydrops fetalis and communicating hydrocephalus
Authors: MacDermot K. D. , Buckley B. , Van Someren V.
Published: July 2010

We describe a single male infant who developed severe hydrops fetalis between 19 and 28 weeks of gestation. After delivery at 32 weeks he was treated by hemofiltration, prolonged ventilation and intravenous feeding. He had hypertelorism, orbital hypoplasia without proptosis, brachy‐dactyly, frontal and temporal bossing of the skull, central hypotonia, communicating hydrocephalus, and severe delay in psychomotor development. Signs of connective tissue disorder included: osteopenia, pathological fracture, yellow/grey discolored teeth, blue sclerae and easy bruising. Laboratory investigations failed to reveal the cause of fetal hydrops or collagen abnormality. His mother and one sib had learning difficulties. Although some of these findings may be due to perinatal factors, the connective tissue abnormalities suggest a genetic syndrome in the heterogeneous group of osteogenesis imperfecta. This case either represents the more severe end of the spectrum of Type IV osteogenesis imperfecta or the mild end of the spectrum of Cole‐Carpenter syndrome.
Mitochondrial gene mutations in familial non‐insulin‐dependent diabetes mellitus in Taiwan
Authors: Chuang Lee‐Ming , Wu Huey‐Peir , Chiu Ken C. , Lai Chuen‐Shiang , Tai Tong‐Yuan , Lin Boniface J.
Published: July 2010

Mitochondrial gene mutations are found to cause certain forms of diabetes mellitus and related syndromes. To study the prevalence of mitochondrial gene mutations in subjects with non‐insulin‐dependent diabetes mellitus (NIDDM) in Taiwan, 23 pedigrees with multiple siblings affected with NIDDM were consecutively collected from patients living in northern Taiwan. The A‐to‐G mutation at position 3243 np in the tRNALeu gene and the mutation at position 8344 were screened by PCR‐RFLP methods and confirmed by direct DNA sequence analysis. Among 23 NIDDM pedigrees, one pedigree was found to carry the 3243 np mutation. There was no 8344 np mutation in this series. Clinical features of this pedigree were consistent with mitochondrial disease in terms of maternal transmission, relatively early onset, non‐obesity, insulin‐requirement and association with hearing impairment. There was no correlation between the degree of heteroplasmy of mitochondrial gene mutation in leukocyte DNA and clinical severity. We conclude that a mitochondrial gene defect is an important genetic factor in familial cases with NIDDM in Taiwan.
A novel missense mutation in exon 3 of the COL4A5 gene associated with late‐onset Alport syndrome
Authors: Turco Alberto E. , Rossetti Sandro , Biasi M. Olivia , Rizzoni Gianfranco , Massella Laura , Saarinen Niina H. , Renieri Allessandra , Pignatti Pier Franco , De Marchi Mario
Published: July 2010

We have identified a novel missense transition (362G→A) in exon 3 of the COL4A5 gene in a male patient with late‐onset Alport syndrome. We used non‐isotopic single strand conformation polymorphism, heteroduplex analysis, and automated DNA sequencing. The mutation changes a conserved glycine at codon 54 for an aspartic acid (Gly54Asp), which abolishes a BstNI site. Using restriction analysis, we identified the heterozygous carrier status in the two daughters of the proband. Our findings are in keeping with the hypothesis that slower progressive forms of Alport syndrome are more often associated with missense mutations rather than large deletions or frameshifts. This is the first mutation described in the N‐terminus triple helical 7S domain of the COL4A5 gene in an Alport syndrome patient.
Christian's spondylo‐digital syndrome: second familial case
Authors: García‐Cruz D. , Cantú J. M. , García‐Martínez F. J. , García‐Cruz M. O. , Nazará Z. , González‐Ulloa B. , Hernández‐Córdova A. , Ruíz M. X. , Sánchez‐Corona J.
Published: July 2010

We studied a mother and daughter with skeletal dysplasia which was characterized clinically by proximal and distal flexion contractures in the phalanges, and by brachydactyly, clinodactyly and ulnar and radial subdislocations of the fingers. Radiologically, the 2nd metacarpal in the daughter was seen to be longer than the other metacarpals, with bone carpal fusion, and flexion contractures of the fingers in both hands. Thoraco‐lumbar xyphorotoscoliosis and malformed vertebrae with dyssegmentation of L2‐L3, T12 and L1 with cuneiform shape, asymmetry of the pelvic bones and exostotic lesions in the proximal third of the tibia and the distal third of the femur were also noted. The clinical and radiological characteristics were compatible with the syndrome described by Christian et al. in 1975 and called the second metatarsal syndrome. The purpose of this paper was to present a second corroborative familial case and to propose another name: Christian's spondylo‐digital syndrome.
Association between a dimorphic site on chromosome 12 and clinical diagnosis of hypertension in three independent populations
Authors: Frossard Philippe M. , Lestringant Gilles G.
Published: July 2010

With the aim of identifying putative quantitative trait loci (QTLs) involved in the regulation of blood pressure, we have carried out association studies at a candidate genetic locus ‐ a human pancreatic phospholipase A2 (PLA2) gene localized on chromosome 12. Positive associations were found between the presence of a Taq I dimorphic site localized in the first intron of this gene and hypertension in three sample populations (two from USA and one from Germany). These results indicate that a QTL implicated in determining an individual's genetic susceptibility to hypertension could be present within up to 30 cM of this human PLA2 gene.
Two brothers with an unbalanced 8;17 translocation and infantile pyloric stenosis
Authors: Hodgson S. V. , Berry A. C. , Dunbar Helen M.
Published: July 2010

Two half‐brothers are described who had developmental delay and minor dysmorphic features, both of whom had operative treatment for pyloric stenosis. They had identical unbalanced karyotypes: 46,XY,‐17,+der(17)t(8;17) (q24;q25). This was inherited from their mother who had the balanced form of the translocation. She was of normal intelligence and had no history of pyloric stenosis herself or in her extended family. It is suggested that the unbalanced chromosomal rearrangement could have been associated with the development of pyloric stenosis in these two brothers.
Partial deletion 11q: report of a case with a large terminal deletion 11q21‐qter without loss of telomeric sequences, and review of the literature
Authors: Hertz Jens Michael , Tommerup Niels , Sørensen Flemming Brandt , Henriques Ulrik V. , Nielsen Alice , Therkelsen Aage J.
Published: July 2010

We describe the cytogenetic findings and the dysmorphic features in a stillborn girl with a large de novo terminal deletion of the long arm of chromosome 11. The karyotype was 46,XX,del(11)(q21qter). By reviewing previous reports of deletion 11q, we found that cleft lip and palate are most frequently seen in proximal 11q deletions involving 11q21. Telomeric staining using the PRINS technique demonstrated normal telomeric sequences in the deleted chromosome 11.
Course of autosomal recessive polycystic kidney disease (ARPKD) in siblings: a clinical comparison of 20 sibships
Authors: Deget F. , Rudnik‐Schöneborn S. , Zerres K.
Published: July 2010

Forty‐two children out of 20 sibships with autosomal recessive polycystic kidney disease were observed pro‐ and retrospectively over a mean period of 3.7 years in a long‐term study on cystic kidney diseases in children. The intra‐ and interfamilial variability in terms of age at diagnosis, administration of antihypertensive therapy, liver affection, and renal function were evaluated. According to the 1971 subclassification of Blyth & Ockenden, defining different grades of severity, 12 patients were assigned to the perinatal, nine to the neonatal, 13 to the infantile, and eight to the juvenile subtype of autosomal recessive polycystic kidney disease. In 11 of the 20 families different subtypes were observed among affected siblings. In seven families, affected sibs belonged to adjacent subtypes, while major intrafamilial differences were observed in only four families. The defined subtypes, therefore, cannot be regarded as appropriate in distinguishing genetic groups of autosomal recessive polycystic kidney disease. With respect to the severity of autosomal recessive polycystic kidney disease, there is a wide spectrum of phenotypic manifestations, ranging from stillbirths to mildly affected adults, while intrafamilial variability of the clinical picture is generally small with multiple allelism as the most likely genetic explanation. Age at death, however, showed gross variation in eight sibships. Differences in the clinical course between several siblings cannot be explained by a sex influence in autosomal recessive polycystic kidney disease.
18p monosomy with GH‐deficiency and empty sella: good response to GH‐treatment
Authors: Schober E. , Scheibenreiter S. , Frisch H.
Published: July 2010

A patient with 18p monosomy and GH deficiency due to pituitary hypoplasia, who showed an excellent response to GH‐treatment, is described. Patients with this syndrome should be considered for endocrine evaluation, as they can benefit from hormonal substitution.
On two patients with and without the classical Wolf‐Hirschhorn syndrome (WHS) sharing the same chromosome 4p16.3 specific probe deletion: evidence of a contiguous gene deletion syndrome
Authors: Petit P. , Schmit J. , Van den Berghe H. , Fryns J. P.
Published: July 2010

We report here on phenotype‐karyotype correlations in two patients with and without complete features of the WHS but sharing the lack of a specific cosmic probe (D4S96/D4Z1) from 4p16.3. These findings indicate that WHS is true a contiguous gene deletion syndrome in nature and expression.
The molecular characterization of Gaucher disease in South Africa
Authors: Morar Bharti , Lane Anthony B.
Published: July 2010

DNA from 29 southern African Gaucher disease patients was analyzed for five common Gaucher disease mutations: 1226G, 1448C, 84GG, IVS2 + 1 and 1504T. The origins of the patients were as follows: 14 Ashkenazi Jews; 6 Gentile Caucasoids; 8 Negroids; and one of mixed ancestry. The 1226G allele accounted for 80% of disease alleles in the Jewish patients, 50% of alleles in the Gentile Caucasoid patients and was absent from the Negroid patients. The 1448C allele was present in both the Jewish (1 of 24 alleles) and Negroid patients (3 of 16 alleles). Single‐strand conformation polymorphism analysis was successfully used to detect mutation 1226G. This system also revealed the presence of mutation 1297T in a Jewish patient and a novel point mutation, 1277T, in an Afrikaans‐speaking Caucasoid patient. Screening of 360 unrelated, healthy Ashkenazi Jewish volunteers to estimate the frequency of disease alleles in the local population led to the detection of 17 carriers: 16 possessed the 1226G allele (frequency = 0.0222), and one the 1297T allele (frequency = 0.0014). Using these results, together with the fact that only 92% of “Gaucher alleles” would be detected in this study, we estimate the disease carrier frequency in the Ashkenazim of South Africa to be 0.05, or approximately 1:20. A reliable carrier screening programme can now be offered to the local Jewish community. The majority of the disease alleles in the two Gentile groups remain uncharacterized.
X‐linked exudative vitreoretinopathy caused by an arginine to leucine substitution (R121L) in the Norrie disease protein
Authors: Johnson Kimberly , Mintz‐Hittner Helen A. , Conley Yvette P. , Ferrell Robert E.
Published: July 2010

We report the cosegregation of an arginine to leucine substitution at position 121 of the Norrie disease protein in a large kindred where exudative vitreoretinopathy segregates as an X‐linked recessive trait. The clinical phenotype and rate of disease progression were extremely variable, with progression to total retinal detachment from less than age 2 years to more than 21 years. To date, all mutations in X‐linked vitreoretinopathy have been missense mutations, presumably not affecting the three‐dimensional structure of the NDP gene product, and clustered around residues 121–126 of the Norrie protein. This contrasts with the diversity of mutations seen in the more severe, allelic Norrie disease.
Mitotic and meiotic stability of the CAG repeat in the X‐linked spinal and bulbar muscular atrophy gene
Authors: Watanabe M. , Abe K. , Aoki M. , Yasuo K. , Itoyama Y. , Shoji M. , Ikeda Y. , Iizuka T. , Ikeda M. , Shizuka M. , Mizushima K. , Hirai S.
Published: July 2010

X‐linked spinal and bulbar muscular atrophy (SBMA) occurs due to an expansion of the trinucleotide repeat (CAG)n in the androgen receptor gene. Anticipation is relatively rare in SBMA in contrast to spinocerebellar ataxia type 1 (SCA1), and dentatorubral and pallidoluysian atrophy (DRPLA) which show obvious paternal anticipation. The differences in the CAG repeat number were compared among sperm, leukocytes and skeletal muscles of SBMA patients. In SBMA, the sperm of most patients and the skeletal muscle of all patients showed the same repeat number as their leukocytes, whereas the increase in the repeat number from leukocytes to sperm was evident in SCA1 and DRPLA patients. The higher mosaicism level in sperm compared with leukocytes was common in SBMA, SCA1 and DRPLA, and the level of sperm was lower in SBMA than in SCA1 and DRPLA. Thus, spermatogenesis was suggested to be strongly associated with paternal anticipation. The mosaicism level was smaller in SBMA than in other (CAG)n expanded disorders, and smallest in the SBMA carrier females. These findings demonstrate that the CAG repeat in SBMA is relatively stable in mitotic and meiotic processes, and there is a possibility that the lower mosaicism level of the carrier females compared with the SBMA patients is associated with X‐linked recessive inheritance.
A cystic fibrosis patient homozygous for 621 + 1G→T mutation has a severe pulmonary disease, mild pancreatic insufficiency and a gastro‐esophageal reflux
Authors: Witt Michal , Pogorzelski Andrzej , Zebrak Jerzy , Rutkiewicz Ewa
Published: July 2010

A cystic fibrosis patient homozygous for 621 + 1G→T mutation of the CFTR gene has been identified during a molecular screening program of Polish CF families. The patient is currently a 21‐year‐old female with severe pulmonary involvement, mild pancreatic insufficiency and complicated gastroesophageal reflux.
Triphalangeal thumb and brachyectrodactyly syndrome: an uncommon entity with evidence of geographic distribution
Authors: Zenteno J. C. , Aguinaga M. , Chavez V. , Sastré N. , Rivera M. R. , Kofman‐Alfaro S.
Published: July 2010

A new Mexican family with the triphalangeal thumb‐brachyectrodactyly syndrome is described. The proposita, a 17‐year‐old female, showed the classic malformation pattern: triphalangeal thumb, brachysyndactyly in the hands and ectrodactyly in the feet. Several members of the family had similar malformations, and others presented minor manifestations of the disease (brachydactyly and nail dysplasia). This is the fourth familial case reported in the literature with the triphalangeal thumb and brachyectrodactyly complex and the third of Mexican origin, reflecting a geographical predominance in the occurrence of this uncommon pathology.
Familial Alzheimer's disease co‐segregates with a Met 146 Ile substitution in presenilin‐1
Authors: Jørgensen Poul , Bus Claus , Pallisgaard Niels , Bryder Marianne , Jørgensen Arne Lund
Published: July 2010

The presenilin‐1 (PS‐1)/S 182 gene at chromosome 14q24.3 is, when mutated, the most common disease gene in autosomal dominant early‐onset Alzheimer's disease. Substitution of methionine 146 of the gene product for either valine or leucine co‐segregates with Alzheimer's disease with the age of onset in the late thirties or early forties. Here we describe a new substitution of methionine 146 for isoleucine that co‐segregates with Alzheimer's disease with age of the onset in the early forties. All identified missense mutations in methionine codon 146 replace one hydrophobic amino acid (Met) with another (Val, Leu, Ile) and correspond to any nucleotide change at the first or third position of the codon. Second position mutations invariably lead to replacement of the hydrophobic methionine with a hydrophilic amino acid that may severely affect the function of the protein. The fact that no second position mutations have been identified so far may support the hypothesis that the protein product of PS‐1 plays a crucial role during development.
Late juvenile metachromatic leukodystrophy (MLD) in three patients with a similar clinical course and identical mutation on one allele
Authors: Tylki‐Szymanska Anna , Berger Johannes , Löschl Beate , Lugowska Agnieszka , Molzer Brunhilde
Published: July 2010

Metachromatic leukodystrophy (MLD) is an autosomal, recessively inherited, lysosomal storage disease caused by arylsulfatase A (ASA) activity deficit. Arylsulfatase A initiates the degradation of sulfatide (cerebroside sulfate), which is an essential component of myelin. The main clinical symptoms are caused by progressive demyelination. At least 37 MLD‐related ASA mutations are known to date. I179S (E3P799) is a disease‐related mutation, described for the first time by Fluharty in 1991. This aberration appears to substantially reduce, but not completely eliminate ASA activity, and was detected in individuals with late‐onset (juvenile or adult) forms of MLD. This paper deals with the peculiar clinical course in three unrelated juveniles with late‐onset MLD carrying the I179S mutation on one allele. In the three described patients with the I179S mutation, psychiatric disturbances and intellectual impairment dominated the clinical picture, while the neurological lesions progressed more slowly. Although the symptoms appeared rather early, making it possible to classify this as the juvenile type of MLD, the clinical picture was more that of the adult type. Although the mutations on the second allele in our patients are unknown, one can speculate, that the mutation I179S plays an important role in the characteristic clinical course (psychiatric impairment, slower neurological deterioration, but relatively early onset). It seems that I179S mutation on one allele with another mutation on the other allele reduces ASA activity, but the enzyme can still cope with a part of the substrate influx, leading to late‐juvenile‐onset MLD with such strikingly similar phenotypes remaining a little bit of the adult (psychiatric) type. This could be one more argument in favour of phenotype‐genotype correlation in patients with MLD.
Apolipoprotein E4allele in the normal elderly: neuropsychologic and brain MRI correlates
Authors: Schmidt H. , Schmidt R. , Fazekas F. , Semmler J. , Kapeller P. , Reinhart B. , Kostner G. M.
Published: July 2010

The presence of the apolipoprotein E e4 allele has been considered to be a risk factor for Alzheimer's disease and vascular dementia. We therefore used demanding neuropsychologic testing and brain MRI to determine if elderly normals with at least one e4 allele demonstrate subclinical changes in cognition and a higher frequency of brain atrophy or silent ischemic brain damage. The study population consisted of 214 randomly selected individuals aged 50 to 75 years without neuropsychiatric or general disease. There were 175 (81.8%) subjects without and 39 (18.2%) with at least one e4 allele. The two groups were comparable for age, length of education, verbal intelligence, mood and major vascular risk factors. Apolipoprotein E e4 carriers performed significantly worse than non‐carriers when assessed for learning and memory abilities, while there were no differences in test results of conceptualization, attention, speed of mental processing and visuopractical skills. There were no between‐group differences for thromboembolic and lacunar infarcts, white matter hyperintensity grading and the semiautomatically measured white matter hyperintensity area. The extent of sulcal and ventricular widening as well as hippocampal and parahippocampal volumes were also similar between the comparative subsets. We conclude that the apolipoprotein E e4 allele is associated with subtle learning and memory deficits in normal elderly persons and may therefore be suggested a marker for accelerated cognitive aging. In this group of subjects it was not associated with brain parenchymal changes as demonstrated by MRI.
Trisomy 13/trisomy 18 mosaicism in an infant
Authors: Abe K. , Itoh N. HaradaU , Hirakawa O. , Niikawa N.
Published: July 2010

Cytogenetic analysis of amniotic fluid cells from a 31‐week‐old fetus suffering from polyhydramnios revealed that there were two cell lines, each with either trisomy 13 or trisomy 18. We studied the origin and mechanism of formation of this unique mixoploidy by tracing chromosomal heteromorphisms as genetic markers, and showed no discordance of parent‐child transmission between the two cell lines in any of the heteromorphisms examined. The result indicated that the mixoploidy is not chimerism but mosaicism and that the mechanism of mosaic development is most likely due to two non‐disjunctional events which had occurred independently at the two‐cell stage of the zygote. A girl was born at the 38th gestational week and her clinical features were mainly those for trisomy 13. Chromosome analysis of the newborn confirmed +13/+18 mosaicism in fibroblasts from the skin and chorionic plate, while cord blood lymphocytes and chorionic villus cells showed only the +18 cell line.
Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p in fetuses with holoprosencephaly
Authors: Chen Chih‐Ping , Liu Fen‐Fen , Jan Sheau‐Wen , Lin Chen‐Li , Lan Chung‐Chi
Published: July 2010

Chromosome aberrations, mendelian mutations and exogenous agents can cause holoprosencephaly. Therefore, etiologic evaluation of holoprosencephaly is necessary for obstetricians and genetic counselors, once a prenatal diagnosis of holoprosencephaly has been made. We present four pregnancies in three women in which routine sonographic examinations led to the prenatal diagnosis of holoprosencephaly. Prenatal cytogenetic analysis and fluorescence in situ hybridization demonstrated a 46, XY, del(7)(pter→q32:) and a 46, XY, der(2)t(2;3)(q37;p21)pat karyotype respectively in two fetuses with cyclopia, and a 46, XX, der(2)t(2;3)(q37;p21)pat and a 46, XX, der(7)t(3;7)(p23;q36) karyotype respectively in two fetuses with premaxillary agenesis. In conclusion, terminal deletion 7q and partial trisomy 3p in holoprosencephalic fetuses indicates that genes contributing to craniofacial development reside in these critical regions. Proper prognostic evaluation in further pregnancies requires expertise in cytogenetics and genetic counseling.
Cord blood immunoglobulin E in like‐sexed monozygotic and dizygotic twins
Authors: Husby S. , Holm N. V. , Christensen K. , Skov R. , Morling N. , Petersen P. H.
Published: July 2010

Genetic and environmental factors have been implicated in the etiology of atopy and of serum IgE levels. In order to eliminate post‐natal environmental influences we measured IgE in cord blood (CB‐IgE) from a cohort of unselected, like‐sexed twins. IgE determination was performed with a sensitive radioimmunoassay with a detection limit of 0.01 kU/l. Samples with contamination by maternal blood were identified by IgA determination and excluded. CB‐IgE was evaluated in 29 monozygotic (MZ) and 28 dizygotic (DZ) twin pairs. The means and variances for IgE values were comparable for MZ and DZ twins when sex was controlled for. Placental anatomy (MZ twins with mono‐and dichorial placenta and DZ twins with one or two placentae) had no significant influence on the IgE levels. In an analysis of variance with subsampling the among‐pair, within‐pair and analytical variance components were calculated. The analytical variance was well below the biological variances. Biometrical analysis showed that the best model by Akaike Information Criteria was a model including only additive genetic and non‐shared environmental factors. With this model the heritability estimate was 0.8. These data suggest that the majority of the variation in CB‐IgE is accounted for by genetic factors, but a substantial effect of a common environment cannot be excluded with the present sample size.
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLO‐SL): a genealogical study of Swedish families of probable Finnish background
Authors: Nylander P.‐O. , Drugge U. , Holmgren G. , Adolfsson R.
Published: July 2010

Four Swedish families in northern Sweden with polycystic lipomembranous ostodysplasia (PLO‐SL) were studied genealogically. Historical and genealogical data provided evidence for a Finnish origin. Both parents of two of the families could be traced back to Finnish ancestors, and the other two families had a common origin in a region with a known Finnish influence, but without evidence for Finnish ancestry. PLO‐SL is the first rare monogenic disease with an autosomal recessive inheritance in Sweden with a probable Finnish origin.
Cerebral defects confirm midline developmental field disturbances in supernumerary der(22), t(11;22) syndrome
Authors: Pallotta R. , Fusilli P. , Ehresmann T. , Cinti R. , Verrotti A. , Morgese G.
Published: July 2010

We describe a girl with midline defects and distal limb anomalies, who had a supernumerary der(22) syndrome. The presence of some anomalies identifying the midline defects, led us to review all patients reported up to now, with interesting results. We point out the particular finding of midline defects in CNS only, in patients studied by autopsy or neuroradiologic imaging.
Partial trisomy 10 mosaicism with cutaneous manifestations: report of a case and review of the literature
Authors: Boon Catherine , Wlarkello Tom , Jackson‐Cook Colleen , Pandya Arti
Published: July 2010

A female infant with partial trisomy 10 mosaicism and hypomelanosis of Ito is presented. Features include a prominent forehead, hypertelorism, large dysplastic ears, prominent nasal root, a cleft lip and alveolar ridge, bilateral metatarsus adductus, and streaks and whorls of hypopigmented skin. The skin findings were diagnostic for hypomelanosis of Ito. A peripheral blood karyotype was normal. Fibroblasts from a junctional skin biopsy revealed mosaicism for partial trisomy of chromosome 10 [46, XX/47, XX, +del(10) (q11.2q23.2)]. The physical findings of this patient are compared to five published cases of complete trisomy 10 mosaicism and 94 cases of isolated trisomy 10p and trisomy 10q.
Distinct facial appearance with nasal hypoplasia, constipation, severe mental retardation and hypotonia in two unrelated young males
Authors: Fryns Jean‐Pierre , Troch Chantal De , Mol Christine Van , Vandenbossche Luc
Published: July 2010

In this report we describe two unrelated young males with severe mental retardation, persisting hypotonia, and constipation. A maternal uncle of one of these two boys died at the age of 18 months and presented the same clinical symptoms. The triad mental retardation, hypotonia, constipation is a characteristic finding in the FG syndrome, an X‐linked mental retardation syndrome. At the present time, there is increasing evidence that the FG syndrome‐phenotype may be present in different XLMR conditions, e.g. the fragile X syndrome. In addition to the triad severe mental retardation, hypotonia, constipation, the present two male index patients had a characteristic facial appearance with nasal hypoplasia, relative microcephaly and pre‐and postnatal overgrowth. The question is raised whether the present two males are examples of a specific entity within the FG‐syndrome‐like phenotype.
Partial monosomy 10q and partial trisomy 9q with anal atresia due to maternal translocation: t(9;10)(q32;q26)
Authors: Tsukuda Toshinori , Nagata Ikuo , Sawada Hiroshi , Murakami Jun , Hanaki Keiichi , Urashima Hirofumi , Kaneda Tomoharu , Shimizu Norio , Kaibara Nobuaki , Kodama Nagao , Ohzeki Takehiko , Shiraki Kazuo
Published: July 2010

We report a case of a boy with a partial deletion of the long arm of chromosome 10 and partial duplication of the long arm of chromosome 9 due to maternal balanced translocation. The karyotype was 46, XY,‐10, +der(10)t(9;10)(q32;q26)mat. Our patient had imperforate anus and as this finding is usually not observed in association with trisomy 9q, it suggests that partial monosomy of the long arm of chromosome 10 might be associated with anogenital anomalies.
Three familial cases presenting with an immobile spine. Rigid spine or Emery‐Dreifuss syndrome?
Authors: Spranger M. , Spranger S. , Ziegan J. , Lössner J. , Meinck H.‐M.
Published: July 2010

A father and his two sons presented with slowly progressive muscular weakness, contractures of the spine, elbows and ankles, and cardiac conduction disturbances in the father. Clinical and histological findings are discussed in relation to the hitherto reported cases of autosomal dominant variant of the Emery‐Dreifuss syndrome and the distinction from the rigid spine syndrome.
COFS syndrome with familial 1;16 translocation
Authors: Temtamy S. A. , Meguid N. A. , Mahmoud A. , Afifi H. H. , Gerzawy A. , Zaki M. S.
Published: July 2010

We report on an Egyptian girl with phenotypic abnormalities of cerebro‐oculo‐facio‐skeletal syndrome. She had microcephaly, bilateral congenital cataract, nystagmus, long ear pinnae, camptodactyly, prominent heels, coxa valga, kyphosis and flexure contracture of the elbows and knees. CT scan showed bilateral symmetrical intracranial calcifications. In addition, she had an apparently balanced translocation: 46, XX, t(1;16)(q23;q13) in all cells transmitted from a phenotypically normal mother with a similar balanced translocation mosaicism. We suggest that genes for COFS syndrome could be located on chromosome 1q23 or 16q 13. We recommend chromosomal analysis and DNA studies in cases with COFS manifestations.
Further evidence for a syndrome of “apple peel” intestinal atresia, ocular anomalies and microcephaly
Authors: Slee Jennie , Goldblatt Jack
Published: July 2010

We report on a male child with “apple peel” atresia, associated with microcephaly, with subsequent hydrocephalus, short stature, moderate global developmental delay and ocular abnormalities. A similar phenotype was previously reported by Stromme et al. in 1993 in female siblings, and this description of another affected individual provides further evidence for this being a distinct syndromic entity.
Mild form of beta‐ketothiolase deficiency (mitochondrial acetoacetyl‐CoA thiolase deficiency) in two Japanese siblings: identification of detectable residual activity and cross‐reactive material in EB‐transformed lymphocytes
Authors: Fukao Toshiyuki , Kodama Akihiko , Aoyanagi Noriyuki , Tsukino Ryu‐ichi , Uemura Shigeru , Song Xiang‐Qian , Watanebe Hiroh , Kuhara Tomiko , Matsumoto I. , Orii Tadao , Kondo Naomi
Published: July 2010

Mitochondrial acetoacetyl‐CoA thiolase (T2) deficiency is an inherited metabolic disorder of isoleucine and ketone body catabolism. We report the cases of two siblings who showed clinically mild forms of this disorder. They did not excrete tiglylglycine in urine. Their EB‐transformed lymphocytes contained residual T2 activity, which was confirmed by immunotitration analysis. In immunoblot analysis, the bands corresponding to T2 in the samples of the cell lines from two patients were the most intensely detected among those from 19 T2‐deficient cell lines tested
A new autosomal recessive syndrome of pachygyria
Authors: Straussberg R. , Gross S. , Amir J. , Gadoth N.
Published: July 2010

Pachygyria is a rare development disorder resulting from impaired neuronal migration. Usually, it is a sporadic phenomenon, but rare dominant or autosomal recessive syndromes are known. This report describes a family in which the parents are first cousins and three of the siblings suffer from moderate mental retardation, pachygyria and strabismus. It is suggested that this is a distinct type of autosomal recessive pachygyria.
Terminal deletion of the long arm of chromosome 4 in a mother and two sons
Authors: Descartes Maria , Keppler‐Noreuil Kim , Knops Judith , Longshore John W. , Finley Wayne H. , Carroll Andrew J.
Published: July 2010

Deletion of chromosome 4q31→pter has been characterized as a distinctive malformation syndrome. We report a mother and two sons with deletion of the long arm (q) of chromosome 4 del(4)(q34.2).
Lack of association of angiotensin I‐converting enzyme gene polymorphism and premature myocardial infarction in Mauritian Indians
Authors: Ramasawmy Rajendranath , Manraj Meera , Kotea Navaratnam , Shun Nathalie Kok , Genin Emmanuelle , Feingold Josué , Krishnamoorthy Rajagopal , Baligadoo Sooriahnarain
Published: July 2010

Eighty‐five young Mauritian Indians, male survivors of premature myocardial infarction (MI) and thus belonging to a high risk group, were compared with 108 stringently selected controls for a possible association between premature MI and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I‐converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group and 0.43 in the control group, and thus no association between I/D polymorphism of ACE with susceptibility to early‐onset MI was found in this population group. Other gene components of the renin‐angiotensin system and lipid metabolism need to be explored to understand the genetic factors involved in causing MI at an early age.
Population variation at the polymorphic ApaLI restriction enzyme site in intron 5 of the WT1 gene
Authors: Besnard‐Guérin Corinne , Winqvist Robert , Newsham Irene , Cavenee Webster K.
Published: July 2010

We examined 63 unrelated individuals from the United States for the ApaLI polymorphism in intron 5 of the WT1 gene. Allele frequencies of 0.13 and 0.87 for the A and B alleles, respectively, and a heterozygosity index of 24% contrast sharply with previous data obtained in the Japanese population where allele frequencies of 0.55 and 0.45 for the A and B alleles and a heterozygosity index of 59% were reported. These data suggest genetic heterogeneity at the WT1 locus, which may contribute to the differences in the incidence of Wilms tumor between the two population groups.
Gaucher disease: studies of phenotype, molecular diagnosis and treatment
Authors: Rice Erin O. , Mifflin Theodore E. , Sakallah Sameer , Lee Robert E. , Sansieri Carol A. , Barranger John A.
Published: July 2010

This report summarizes the results on 39 patients with Gaucher disease who have been genotyped, evaluated, and/or followed at this center. Mutation analysis for 4 common mutations; N370S, L444P, 84gg and IVS2 (+1), was performed for all patients. Mutation analysis identified both mutant alleles in 69% and at least one mutant allele in 90% of all chromosomes. This study group of 39 patients included 32 type 1, four type 2 and three type 3 patients. We include the details of the clinical course of two patients with Gaucher disease treated with enzyme replacement therapy (ERT). One patient with chronic neuronopathic Gaucher disease has been treated with enzyme replacement therapy (ERT) at a dose of 60 U/kg every 2 weeks since 2.5 years of age and has shown no progression of neurologic involvement. A second patient with non‐neuronopathic Gaucher disease has demonstrated an unusually delayed response to ERT. No clinical response was noted following 17 months of treatment at 60 U/kg every 2 weeks. Only after the dose was increased to 60 U/kg every week was a clinical response evident. Response to treatment at 15 U/kg every 2 weeks was variable in the four type 1 patients treated at the lower dose. In two of these patients with identical genotypes, one patient demonstrated a positive clinical response to low dose treatment while the other patient did not.
Risk estimates for balanced reciprocal translocation carriers — prenatal diagnosis experience
Authors: Barišic Ingeborg , Zergollern Liljana , Mužinic Dubravka , Hitrec Vlasta
Published: July 2010

An analysis was performed on 40 families at risk for an unbalanced rearrangement in the fetus because one of the parents is a reciprocal translocation carrier. The overall risk at second trimester prenatal diagnosis was 14% (8/57). The individual risks for unbalanced offspring at second trimester prenatal diagnoses and at birth were estimated using empirical data by Stengel‐Rutkowski et al. (1988). The risks at birth ranged from 0%–21.6%. Most reciprocal translocations (22 or 55%) were at low risk. Without risk (7 or 17.5%), medium risk (6 or 15%) and high risk (5 or 12.5%) translocations were about equally represented and relatively infrequent. The analysis shows that the mode of ascertainment as well as the measurement of lengths of observed or probable imbalances cannot serve as a reliable risk predictor in individual counselling. In the translocations ascertained through spontaneous abortions the risk is frequently small or nonexistent, but remarkable exceptions to this rule are observed. Translocations discovered through unbalanced offspring were found to belong to different risk groups with the exception of the no risk group. Individual risk estimates have to be performed as a basis of genetic counselling before or during pregnancy so that parents with reciprocal translocations can make their choices regarding the available options.
RYR mutation G1021A (Gly341Arg) is not frequent in Danish and Swedish families with malignant hyperthermia susceptibility
Authors: Fagerlund T. , Øding H. , Bendixen D. , Islander G. , Ranklev‐Twetman E. , Berg K.
Published: July 2010

Malignant hyperthermia (MH) is a pharmacogenetic disorder. Susceptibility to MH (MHS) is presumed to be inherited in an autosomal dominant way. MH crises are triggered by halogenated inhalational anaesthetics and suxamethonium, and may be lethal if not treated early and adequately. Until now, eight mutations in the RYR1 gene have been described as causes of MHS phenotype in various MH families The mutation RYR1 G1021A (Gly341Arg) has been reported to account for approximately 10% of Caucasian MHS cases. However, in our study this mutation was discovered in only 1 out of 89 Scandinavian families, indicating that this mutation may be the cause of MHS in only about 1% of MHS families in those populations. The mutation may have been brought to Scandinavia by an immigrant.
Maternal origin of transferrin receptor positive cells in venous blood of pregnant women
Authors: Slunga‐Tallberg Anna , El‐Rifai Wa'el , Keinänen Mauri , Ylinen Kari , Kurki Tapio , Klinger Katherine , Ylikorkala Olavi , Larramendy Marcelo L. , Knuutila Sakari
Published: July 2010

We studied the origin of transferrin receptor (CD71) positive cells in blood from seven women pregnant with a male fetus in order to explore if fetal cells could be detected among them. We used a technique that allows direct chromosomal analysis by in situ hybridization on immunologically and morphologically classified cells. Enrichment was performed by magnetic activated cell sorting (miniMACS)® using an anti‐CD71 monoclonal antibody. The cells were immunophenotyped by alkaline phosphatase anti‐alkaline phosphatase immunostaining with the same antibody. The origin of the immunophenotyped cells was studied by in situ hybridization using an X cosmid Y repeat chromosome specific probe cocktail. CD71 positive cells were found in six of the seven women at the range of 4 to 43 in respective samples. Over 90% of the CD71 positive cells were nucleated erythrocytes. None of the detected positive cells were shown to be fetal. Thus, the use of transferrin receptor antigen alone in combination with the miniMACS® may not be sufficient for enrichment of fetal cells.