Abstract:
:Bardet-Biedl syndrome (BBS) is a rare pediatric ciliopathy characterized by marked clinical variability and extensive genetic heterogeneity. Typical diagnosis of BBS is secured at a median of 9 years of age, and sometimes well into adolescence. Here, we report a patient in whom prenatal detection of increased nuchal fold, enlarged echogenic kidneys, and polydactyly prompted us to screen the most commonly mutated genes in BBS and the phenotypically and genetically overlapping ciliopathy, Meckel-Gruber syndrome (MKS). We identified the common Met390Arg mutation in BBS1 in compound heterozygosity with a novel intronic variant of unknown significance (VUS). Testing of mRNA harvested from primary foreskin fibroblasts obtained shortly after birth revealed the VUS to induce a cryptic splice site, which in turn led to a premature termination and mRNA degradation. To our knowledge, this is the earliest diagnosis of BBS in the absence of other affected individuals in the family, and exemplifies how combining clinical assessment with genetic and timely assays of variant pathogenicity can inform clinical diagnosis and assist with patient management in the prenatal and neonatal setting.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Ashkinadze E,Rosen T,Brooks SS,Katsanis N,Davis EEdoi
10.1111/cge.12022subject
Has Abstractpub_date
2013-06-01 00:00:00pages
553-9issue
6eissn
0009-9163issn
1399-0004journal_volume
83pub_type
杂志文章abstract::Failure to thrive (FTT) causes significant morbidity, often without clear etiologies. Six individuals of a large consanguineous family presented in the neonatal period with recurrent vomiting and diarrhea, leading to severe FTT. Standard diagnostic work up did not ascertain an etiology. Autozygosity mapping and whole ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13883
更新日期:2020-11-15 00:00:00
abstract::We identified the homozygous p.Arg12* variant in 5 patients with neurodevelopmental delay, but variation databases list many truncating heterozygous variants for this small 2-exon gene. As most of these affect the protein's C-terminus, loss-of-function mediated pathogenicity may be confined to bi-allelic truncating va...
journal_title:Clinical genetics
pub_type: 信件
doi:10.1111/cge.13386
更新日期:2018-10-01 00:00:00
abstract::The Troyer syndrome was found by Cross & McKusick (1967) in 20 members of 12 Old Order Amish families in Holmes County, Ohio; it is a form of hereditary spastic paraplegia combined with distal muscle wasting, i.e. signs of involvement of lower motor neurons. The condition usually begins at 1 to 2 years and progresses ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1976.tb01580.x
更新日期:1976-03-01 00:00:00
abstract::In the Arab population of Kuwait of approximately 1.3 million, 26 cases in 15 families were ascertained to have Bardet-Biedl syndrome (20 cases in 13 families) or Laurence-Moon syndrome (6 cases in 2 families). The apparently increased frequency of these interrelated autosomal recessive syndromes in Arabs is discussed...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1988.tb03414.x
更新日期:1988-02-01 00:00:00
abstract::We present a dysmorphic syndrome in eight males of the same family (four brothers, three cousins and one uncle) that is characterised by: mental retardation, facial dysmorphia, abnormal growth of teeth, skin dimple at the lower back, clinodactyly, patella luxation, malformation of lower limbs, abnormalities of the fun...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1987.tb03297.x
更新日期:1987-11-01 00:00:00
abstract::The syndromic association of striae in the long bones and pelvis, together with sclerosis of the base of the skull, has been investigated in four families. Impairment of hearing and alteration in the shape of the head are the most important clinical manifestations. Spinal abnormalities are an inconsistent feature. The...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1978.tb04250.x
更新日期:1978-02-01 00:00:00
abstract::Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA; MPS IIIA) is caused by a deficiency of the lysosomal enzyme haparan N-sulphatase (NS). The genomic DNA segments of the NS gene from two Chinese patients with MPS IIIA were amplified by polymerase chain reaction, followed by DNA sequencing to study the molecu...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2002.610304.x
更新日期:2002-03-01 00:00:00
abstract::Use of an intragenic BamHI restriction fragment length polymorphism within the 5' end of the retinoblastoma gene (RB1) provided improved genetic counselling for five familial and ten non-familial retinoblastoma patients and their relatives. All other polymorphic probes within RB1 were uninformative in three families, ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1990.tb03488.x
更新日期:1990-02-01 00:00:00
abstract::Two unrelated children with partial deletion of the long arm of a chromosome no. 5 are reported. The boy presented with severe hypotonia, developmental delay, and a few minor defects of the face including frontal bossing, antimongoloid slant of the palpebral fissures, depressed nasal bridge and bilateral epicanthal fo...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1981.tb00692.x
更新日期:1981-03-01 00:00:00
abstract::An allele association study of 19 polymorphisms in surfactant proteins SP-A1, SP-A2, SP-B, and SP-D genes in acute respiratory distress syndrome (ARDS) was carried out. Trend-test analysis revealed differences (p < 0.05) in the frequency of alleles for some of the microsatellite markers flanking SP-B, and for one poly...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2000.580305.x
更新日期:2000-09-01 00:00:00
abstract::In all known congenital imprinting disorders an association with aberrant methylation or mutations at specific loci was well established. However, several patients with transient neonatal diabetes mellitus (TNDM), Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS) exhibiting multilocus hypomethylation...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2010.01514.x
更新日期:2011-07-01 00:00:00
abstract::In this review, we consider the motivation behind contemporary single nucleotide polymorphism (SNP) initiatives. Many of these initiatives are projected to involve large, population-based surveys. We therefore emphasize the utility of SNPs for genetic epidemiology studies. We start by offering an overview of genetic p...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1034/j.1399-0004.2000.580402.x
更新日期:2000-10-01 00:00:00
abstract::Sanfilippo syndrome (mucopolysaccharidosis type III) is the commonest mucoploysaccharidosis. It causes neurodegeneration with often profound sleep and behavioral disturbance. Management of the sleep disturbance is difficult and inconsistent. In this study, we surveyed clinicians with particular expertise in the manage...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2002.620512.x
更新日期:2002-11-01 00:00:00
abstract::There has been a paucity of research into the psychosocial impact of juvenile Huntington's disease (JHD) on the child and the family. The study reported here is part of larger project that aimed to address this and investigate the social and health care needs of those affected by JHD. Ten semistructured interviews wit...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2006.00624.x
更新日期:2006-06-01 00:00:00
abstract::A four generation family with postaxial polydactyly of hands and feet and dental anomalies is reported. Lower and upper incisors were abnormal in shape and number. Additional findings were prominent ear anthelices, hypoplastic and dysplastic nails and mild shortness of stature. Inheritance was dominant with variable e...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1984.tb01108.x
更新日期:1984-12-01 00:00:00
abstract::We investigated the clinical, laboratory, and genetic spectra in Korean patients with dysferlinopathy to clarify its genotype-phenotype correlation. We retrospectively reviewed 101 patients from 96 unrelated families with pathogenic variants of DYSF. The most common initial phenotype was Miyoshi myopathy in 50 patient...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13887
更新日期:2020-11-20 00:00:00
abstract::Steatocystoma Multiplex (S.M.) is an inherited condition characterized by the appearance of cysts during the first or second decade of life. Familial cases have occasionally been reported. We studied 13 patients affected by S.M. from two unrelated families, focusing our attention on HLA, Gm and Km genotypes and on chr...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1989.tb03176.x
更新日期:1989-08-01 00:00:00
abstract::Germline mutations of the STK11 gene mapped to chromosome 19p13.3 are responsible for Peutz Jeghers syndrome (PJS), a dominant disorder associated with characteristic gastrointestinal hamartomatous polyps and a predisposition to various cancers. We conducted a detailed investigation of germline STK11 alterations by pr...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.1999.560207.x
更新日期:1999-08-01 00:00:00
abstract::Twenty-five novel mutations including duplications in the ATP7A gene. Menkes disease (MD) and occipital horn syndrome (OHS) are allelic X-linked recessive copper deficiency disorders resulting from ATP7A gene mutations. MD is a severe condition leading to progressive neurological degeneration and death in early childh...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2010.01461.x
更新日期:2011-03-01 00:00:00
abstract::Phenotypic variations in α-thalassemia mainly depend on the defective α-globin gene number. Genetic modifiers of the phenotype of Hemoglobin H (HbH) disease were poorly reported, apart from β-thalassemia allele that was identified ameliorating the severity of α-thalassemia. Because erythroid Krüppel-like factor (KLF1)...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12443
更新日期:2015-07-01 00:00:00
abstract::This brief account of Woody Guthrie is instructive to clinical geneticists. It tells the story of one famous man's understanding of, and struggle with, Huntington's disease. The philatelic illustration depicts Woody Guthrie playing his guitar in the years before advancement of the disease. ...
journal_title:Clinical genetics
pub_type: 传,历史文章,杂志文章
doi:10.1034/j.1399-0004.2002.610404.x
更新日期:2002-04-01 00:00:00
abstract::Kyphomelic dysplasia is a rare form of generalized skeletal dysplasia with about 15 cases described so far in the literature. We present the clinical, radiological, and pathological findings of an antenatally detected female fetus affected with this disorder. The differential diagnoses of prenatal and perinatal semile...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1034/j.1399-0004.2000.580510.x
更新日期:2000-11-01 00:00:00
abstract::Successful fertilization is fundamental for sexual reproduction. After undergoing a series of molecular and morphological changes, the haploid sperm fuses with the haploid oocyte to create a diploid zygote. Defects in this process might lead to human fertilization failure. We have previously found homozygous mutations...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13505
更新日期:2019-04-01 00:00:00
abstract::436 index patients with major congenital urinary tract malformations, 385 with upper and 51 with lower urinary tract anomalies, were studied. A significant male sex predominance was noted in each group. No apparent correlation was found between parental age, birth order, birth weight and incidence of these malformatio...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1975.tb01952.x
更新日期:1975-07-01 00:00:00
abstract::Type 1a glycogen storage disease (GSD) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Polymerase chain reaction (PCR) and nucleotide sequence analysis were used to identify the location and nature of mutations at the G6Pase locus in two siblings affected with typ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1996.tb02627.x
更新日期:1996-10-01 00:00:00
abstract::A genealogical survey of familial amyloid polyneuropathy in the Arao district of Japan was undertaken, and the data were analysed statistically. The survey revealed 92 patients (46 males and 46 females) in 9 families. Thirty-one of the patients (16 males and 15 females) are alive. For 44 patients, the mean age of onse...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:
更新日期:1983-11-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) usually becomes symptomatic between the third and fifth decades. We studied ten families segregating for ADPKD in which children were observed with typical manifestations of the disease at birth or in early childhood. In these families, linkage analysis was carried ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1989.tb02900.x
更新日期:1989-01-01 00:00:00
abstract::A de novo supernumerary small marker chromosome 15 was observed in a female infant with mental and statomotoric retardation as well as minor facial dysmorphia. The marker chromosome was analyzed by ten different staining techniques and 5-azacytidine treatment of lymphocyte cultures. It is shown that the supernumerary ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1986.tb00570.x
更新日期:1986-07-01 00:00:00
abstract::PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. Thauvin-Robinet et al. (2013) The American Journal of Human Genetics 93: 141-149 SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signalling. Chudasama et al. (2013) The American Journal of Human Genetics 93: 1...
journal_title:Clinical genetics
pub_type: 评论,杂志文章
doi:10.1111/cge.12262
更新日期:2014-03-01 00:00:00
abstract::GNE myopathy or hereditary inclusion body myopathy (HIBM) is an ultra-rare severely disabling autosomal recessive adult onset muscle disease which affects roughly one to three individuals per million worldwide. Genetically, HIBM is caused by mutations in the glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine k...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12086
更新日期:2013-12-01 00:00:00