Abstract:
:The Hartnup mutation affects an amino acid transport system of intestine and kidney used by a large group of neutral charge alpha-amino acids (six essential and several nonessential). We compared developmental outcomes and medical histories of 21 Hartnup subjects, identified through newborn screening, with those of 19 control sibs. We found no significant differences in means of growth percentiles and IQ scores between Hartnup and control groups (but all low academic performance scores were found in the Hartnup group, and various skin lesions occurred in five Hartnup subjects), no significant difference between means of the summed plasma values for amino acids affected by the Hartnup gene in Hartnup and control groups, two Hartnup subjects with clinical manifestations--impaired somatic growth and IQ in one, impaired growth and a "pellagrin" episode in the other--who had the lowest summed plasma amino acid values in the Hartnup group; the corresponding values for their sibs were the low outliers in the control group, and two tissue-specific forms of the Hartnup (transport) phenotype: renal and intestinal involvement (15 families) and renal involvement alone (one family), both forms having been inherited as autosomal recessives (the symptomatic probands had the usual form). Whereas deficient activity of the "Hartnup" transport system is monogenic, the associated plasma amino acid value (measured genotype) is polygenic. The latter describes the parameter of homeostasis and liability to disease. Cause of Hartnup disease is multifactorial.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Scriver CR,Mahon B,Levy HL,Clow CL,Reade TM,Kronick J,Lemieux B,Laberge Csubject
Has Abstractpub_date
1987-05-01 00:00:00pages
401-12issue
5eissn
0002-9297issn
1537-6605journal_volume
40pub_type
杂志文章abstract::The mutations in one-third of Duchenne and Becker muscular dystrophy patients remain unknown, as they do not involve gross rearrangements of the dystrophin gene. We now report a defect in the splicing of precursor mRNA (pre-mRNA), resulting from a maternally inherited mutation of the dystrophin gene in a patient with ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::We determined the mutation spectrum of the RP2 and RPGR genes in patients with X-linked retinitis pigmentosa (XLRP) and searched for correlations between categories of mutation and severity of disease. We screened 187 unrelated male patients for mutations, including 135 with a prior clinical diagnosis of XLRP, 11 with...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/379379
更新日期:2003-11-01 00:00:00
abstract::Several dysmorphic syndromes affect the development of both the eye and the ear, but only a few are restricted to the eye and the external ear. We describe a developmental defect affecting the eye and the external ear in three members of a consanguineous family. This syndrome is characterized by ophthalmic anomalies (...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.03.007
更新日期:2008-05-01 00:00:00
abstract::Several RFLPs have been detected using a cDNA fragment encoding the amino-terminal half of the A subunit of factor XIII. The RFLPs show little linkage disequilibrium and form many different haplotypes that can be used to identify chromosomes transmitting factor XIII A subunit deficiency. Southern blot analysis of thre...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::One of the human urinary ribonucleases (RNases) was isolated and purified to homogeneity (SDS-PAGE) by means of a series of column chromatographies. The enzyme, designated RNase 1, is a glycoprotein with a molecular weight of approximately 16,000. Rabbit antibody to the purified RNase 1 reacted with human urine and se...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract::Association studies offer an exciting approach to finding underlying genetic variants of complex human diseases. However, identification of genetic variants still includes difficult challenges, and it is important to develop powerful new statistical methods. Currently, association methods may depend on single-locus an...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/511312
更新日期:2007-02-01 00:00:00
abstract::We report on the identification of a 0.3 Mb inherited recurrent but variable copy-number gain at Xq28 in affected males of four unrelated families with X-linked mental retardation (MR). All aberrations segregate with the disease in the families, and the carrier mothers show nonrandom X chromosome inactivation. Tiling ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2009.10.019
更新日期:2009-12-01 00:00:00
abstract::Classical genetic approaches for interpreting variants, such as case-control or co-segregation studies, require finding many individuals with each variant. Because the overwhelming majority of variants are present in only a few living humans, this strategy has clear limits. Fully realizing the clinical potential of ge...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2017.07.014
更新日期:2017-09-07 00:00:00
abstract::We describe a new user-intense-learning experience that incorporates the teaching of clinical and research applications of human genetics in biochemistry while training first-year medical students to develop skills in computer access to the literature. Human genetics was incorporated into the biochemistry curriculum b...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::We report here the genetic cause of the X-linked syndrome of psychosis, pyramidal signs, and macro-orchidism (PPM-X) in a three-generation family manifesting the disorder as a mutation in the methyl-CpG binding-protein 2 (MECP2) gene in Xq28. The A140V mutation was found in all affected males and all carrier females i...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/339553
更新日期:2002-04-01 00:00:00
abstract::Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluate...
journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
doi:10.1016/j.ajhg.2014.11.011
更新日期:2015-01-08 00:00:00
abstract::The critical importance of cytoskeletal function for correct neuronal migration during development of the cerebral cortex has been underscored by the identities of germline mutations underlying a number of human neurodevelopmental disorders. The proteins affected include TUBA1A, a major alpha-tubulin isoform, and micr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2009.10.007
更新日期:2009-11-01 00:00:00
abstract::Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic condition characterized by ocular, cutaneous, and central nervous system anomalies. Key clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, and central nervous system lipomas. Seizures, spasticity, and intellectu...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.02.006
更新日期:2016-03-03 00:00:00
abstract::It has been proposed that gluten sensitive enteropathy (GSE) results from the interaction of two loci: one locus linked to HLA and associated with dominant inheritance, and the other, a non-HLA-linked GSE-associated B-cell alloantigen, exhibiting recessive inheritance. We have shown in previous analyses that a two-loc...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::Supernumerary marker chromosomes (SMCs) of chromosome 15, designated "SMC(15)s," are the most common SMC in humans, accounting for as much as 60% of all those observed. We report the characterization of 46 large SMC(15)s, using both fluorescence in situ hybridization and polymerase chain reaction analysis within and d...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/379155
更新日期:2003-11-01 00:00:00
abstract::The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neurodegenerative disorders, has been mapped to chromosome 14q32.1. ADCA type I patients from families segregating SCA3 share clinical features in common with tho...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::The original family with the Allan-Herndon type of X-linked mental retardation has been investigated for linkage by using DNA probes spanning the length of the X chromosome. Available for study, over 3 generations, were 13 affected males, three obligate carriers, and three normal sons of the obligate carriers. Initial...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.08.002
更新日期:2008-09-01 00:00:00
abstract::Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive pancytopenia, congenital malformations, and predisposition to acute myeloid leukemia. At least five complementation groups (FA-A-FA-E) have been identified. The relative prevalence of FA-A has been estimated at an average of approximate...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301632
更新日期:1997-12-01 00:00:00
abstract::Cone-rod dystrophy (CRD) and retinitis pigmentosa (RP) are clinically and genetically overlapping heterogeneous retinal dystrophies. By using homozygosity mapping in an individual with autosomal-recessive (ar) RP from a consanguineous family, we identified three sizeable homozygous regions, together encompassing 46 Mb...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.11.015
更新日期:2012-01-13 00:00:00
abstract::A modified alpha-N-acetylgalactosaminidase (NAGA) with alpha-galactosidase A (GLA)-like substrate specificity was designed on the basis of structural studies and was produced in Chinese hamster ovary cells. The enzyme acquired the ability to catalyze the degradation of 4-methylumbelliferyl-alpha-D-galactopyranoside. I...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2009.09.016
更新日期:2009-11-01 00:00:00
abstract::We have evaluated eight patients with pigmentary anomalies reminiscent of incontinentia pigmenti or hypomelanosis of Ito. All demonstrated abnormal lymphocyte karyotypes with chromosomal mosaicism in lymphocytes and/or skin fibroblasts. In seven the skin was darkly pigmented, and in all of these seven cases the abnorm...
journal_title:American journal of human genetics
pub_type: 杂志文章,评审
doi:
更新日期:1989-08-01 00:00:00
abstract::Five RFLPS of X-linked coagulation factor IX were evaluated in more than 500 normal persons (723-804 X chromosomes) of both sexes who belonged to eight ethnic groups: Anglo-Americans, Basques, Swedes, African-Americans, East Africans, East Indians, Chinese, and Malays. The polymorphisms, 5' to 3', were BamHI, XmnI, Ta...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, loca...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Ichthyosis prematurity syndrome (IPS) is an autosomal-recessive disorder characterized by premature birth and neonatal asphyxia, followed by a lifelong nonscaly ichthyosis with atopic manifestations. Here we show that the gene encoding the fatty acid transport protein 4 (FATP4) is mutated in individuals with IPS. Fibr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2009.06.021
更新日期:2009-08-01 00:00:00
abstract::Waardenburg anophthalmia syndrome, also known as microphthalmia with limb anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here we show that this disease is heterogeneous by reporting on a consanguineous family, ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2010.12.002
更新日期:2011-01-07 00:00:00
abstract::The design and feasibility of whole-genome-association studies are critically dependent on the extent of linkage disequilibrium (LD) between markers. Although there has been extensive theoretical discussion of this, few empirical data exist. The authors have determined the extent of LD among 38 biallelic markers with ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/316906
更新日期:2000-12-01 00:00:00
abstract::Ten cases of small ring chromosomes which did not stain with distamycinA/DAPI and did not possess satellite regions associated with nucleolus-organizing regions are described. In situ hybridization with a battery of biotinylated pericentric repeat probes specific either for individual chromosomes or for groups of chro...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract::Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.10.001
更新日期:2019-12-05 00:00:00
abstract::Dominant congenital spinal muscular atrophy (DCSMA) is a disorder of developing anterior horn cells and shows lower-limb predominance and clinical overlap with hereditary spastic paraplegia (HSP), a lower-limb-predominant disorder of corticospinal motor neurons. We have identified four mutations in bicaudal D homolog ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.04.018
更新日期:2013-06-06 00:00:00