摘要:

Objective:To reevaluate previous claims that non‐syndromic macrocephaly is usually inherited as an autosomal dominant trait. Design: Head size was measured in the parents and sibs of children with non‐syndromic macrocephaly. Outcome measures: If autosomal dominant inheritance is involved, the frequency distribution should be bimodal. Results: Head circumference of parents and sibs of the macrocephalic probands had a mean significantly greater than the population norm, and a unimodal distribution. Probands with psychomotor impairment had bigger heads, and more had a history of birth difficulty, than did unimpaired probands. Conclusions: The usual genetic basis for non‐syndromic macrocephaly is multifactorial with a polygenic genetic basis, rather than autosomal dominant. Risk of recurrence appears to be much lower than if it would be on the assumption ot autosomal dominant inheritance. Macrocephaly in a parent or sib of an unborn child may present a risk for birth injury to that child. A larger series of patients will be necessary | to resolve this que

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02349.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We present the phenotypic, cytogenetic and molecular findings in two dysmorphic and mentally retarded brothers with disomy Xq12→q13.3. The mother and the grandmother carry the same rearrangement of the X chromosome, which was interpreted as an inverted insertion of the segment (X)(q12→q13.3) into Xq21.2. The X‐inactivation‐specific‐transcript (XIST) is expressed in the probands' mother but is absent in her son, confirming the hypothesis that X inactivation is realized only if two X inactivation centers reside on different X‐chromosomes (trans‐configuration). In the phenotypically normal mother the aberrant X chromosome was late replicating in all cells, indicating functional monosomy of the constitutional segment trisomy. The phenotype of the brothers is considered to be the consequence of a functional disomy Xq12→q13.3. The trait combination observed in the brothers was compared with the spectrum of clinical and anthropological traits for proximal Xq disomy in males, elaborated by phenotype analyses of the available l

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02350.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

While congenital anomalies have been identified as the second leading cause of infant mortality among American Indians and Alaska Natives, limited information exists concerning the morbidity of such malformations. This study was undertaken to address this concern. Using data from the national hospital discharge database of the Indian Health Service, for the years 1980–1988, morbidity rates of seven, relatively common and easily identifiable midline malformations among liveborn infants in this minority population were estimated. The seven congenital anomalies and the estimated rates per 10000 births were: neural tube defects 8.09; oral clefts 29.03; abdominal wall defects 2.99; tracheoesophageal fistula 1.86; conotruncal heart defects 5.90; rectal atresia 3.15; and diaphragmatic hernia 3.24. Seven cases (1.1%) had two midline defects reporte

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02351.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

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 uncharac

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02352.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

A presumed right not to know has been claimed in several discussions about testing for genetic diseases or genetic risks in families of populations. In this paper, ethical problems arising from the implementation of a possible right not to know are examined.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02353.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Genotyping with flanking DNA markers was used to ascertain Treacher Collins Franceschetti syndrome (TCOF1) in a subject affected by tetralogy of Fallot and cryptorchidism. The proband's family consisted of a father and sister who were affected by the disease, and a healthy mother. Since cardiac malformation and cryptorchidism have been associated with the TCOF1 syndrome, the proband was suspected to be a carrier of the mutated gene. Microsatellite markers D5S527, SPARC and D5S519, which previously mapped the TCOF1 gene within a 2.1‐cM interval on chromosome 5 (5q32–33.1), were used to follow the transmission of the TCOf 1 mutated locus. Flanking markers D5S519 and D5S527 were informative and enabled us to exclude inheritance of a TCOF1 mutation to the proband, while showing that cardiac malformation and cryptorchidism were unrelated in mis pati

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02354.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We report on Poland sequence observed in two siblings (a girl and a boy) in the same family. This suggests an inheritance pattern consistent with an autosomal recessive or dominant trait transmission with reduced penetrance.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02355.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We report on a case ofde novodirect duplication for the distal part of chromosome 3p: 46, XY, dir dup (3) (p25→pter). At the age of 4 years and 7 months, the boy presented with moderate growth and mental retardation, muscular hypotonia, hypoplasia of the left kidney, a short neck, and a square‐shaped face characterized by a broad and flat nasal bridge, slight epicanthus, and full cheeks. So far, only a few cases with such a small distal 3p duplication have been described, and none of them has ade novodirect duplication for this region. In our patient, dysmorphic signs are less impressive, and developmental delay is relatively moder

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02356.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The reliable evaluation of chromosomal mosaics is still considered to be difficult in clinical diagnosis if aberrant metaphases are only present at low frequencies. Classical cytogenetic findings cannot significantly exclude low mosaic levels, obviously, because of the relatively low number of analyzed metaphases. To study this problem, the number of gonosomes in lymphocyte interphase nuclei was determined by FISH (fluorescencein situhybridization) application of two satellite DNA probes, DXZ1 and DYZ1. The results obtained with this method from lymphocytes of clinically and cytogenetically inconspicuous persons showed a high degree of reliability. The DNA probe yielded correct signals in more than 95% of the analyzed nuclei. Additionally, patients were examined who showed cytogenetically confirmed numerical gonosome aberrations. These results were compared with those obtained from the control group of inconspicuous patients and discussed with respect to the evaluation of gonosomal mosaics.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02357.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Fortuitously, within a 1‐month period, we were referred two individuals for routine cytogenetic amniocenteses involving one chromosome 21 from each patient, which had apparently lost the entire short arm and a major portion of the centromeric alphoid sequences in their amniocytes. Breakage may have occurred within alphoid sequences resulting in extreme variants. Variations of a similar nature were originally referred to as Christchurch (Ch1) chromosomes and have been wrongly determined to be abnormal. The 21p—chromosome variants were similar in both cases, though they are from unrelated individuals. These rare variants, whose origins were both maternal and have no clinical consequences, were characterized by the FISH‐technique to provide a greater degree of cert

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02358.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY