Abstract:
:NALCN is a conserved cation channel, which conducts a permanent sodium leak current and regulates resting membrane potential and neuronal excitability. It is part of a large ion channel complex, the "NALCN channelosome", consisting of multiple proteins including UNC80 and UNC79. The predominant neuronal expression pattern and its function suggest an important role in neuronal function and disease. So far, biallelic NALCN and UNC80 variants have been described in a small number of individuals leading to infantile hypotonia, psychomotor retardation, and characteristic facies 1 (IHPRF1, OMIM 615419) and 2 (IHPRF2, OMIM 616801), respectively. Heterozygous de novo NALCN missense variants in the S5/S6 pore-forming segments lead to congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD, OMIM 616266) with some clinical overlap. In this study, we present detailed clinical information of 16 novel individuals with biallelic NALCN variants, 1 individual with a heterozygous de novo NALCN missense variant and an interesting clinical phenotype without contractures, and 12 individuals with biallelic UNC80 variants. We report for the first time a missense NALCN variant located in the predicted S6 pore-forming unit inherited in an autosomal-recessive manner leading to mild IHPRF1. We show evidence of clinical variability, especially among IHPRF1-affected individuals, and discuss differences between the IHPRF1- and IHPRF2 phenotypes. In summary, we provide a comprehensive overview of IHPRF1 and IHPRF2 phenotypes based on the largest cohort of individuals reported so far and provide additional insights into the clinical phenotypes of these neurodevelopmental diseases to help improve counseling of affected families.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Bramswig NC,Bertoli-Avella AM,Albrecht B,Al Aqeel AI,Alhashem A,Al-Sannaa N,Bah M,Bröhl K,Depienne C,Dorison N,Doummar D,Ehmke N,Elbendary HM,Gorokhova S,Héron D,Horn D,James K,Keren B,Kuechler A,Ismail S,Issa MYdoi
10.1007/s00439-018-1929-5subject
Has Abstractpub_date
2018-09-01 00:00:00pages
753-768issue
9eissn
0340-6717issn
1432-1203pii
10.1007/s00439-018-1929-5journal_volume
137pub_type
杂志文章相关文献
HUMAN GENETICS文献大全abstract::The X chromosomes of individuals with isolated steroid sulphatase deficiency (X-linked ichthyosis) from ten families were studied by flow karyotype analysis. In four of the families, a small but significant reduction in the relative fluorescence of the X chromosome was detected consistent with a deletion ranging from ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291709
更新日期:1988-05-01 00:00:00
abstract::Recently the defective gene locus in seven Caucasian families with the Romano-Ward form of long QT syndrome (LQT) has been mapped to chromosome 11p. To understand the molecular basis of LQT in Chinese, a three-generation family was investigated. Fourteen family members were studied and five individuals were diagnosed ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00201594
更新日期:1994-10-01 00:00:00
abstract::In a pilot study, the possible influence of the inherited electroencephalogram (EEG) pattern on aspects of psychologic maturation was investigated. The twin sample consisted of 208 pairs, 110 monozygotic (MZ) and 98 dizygotic (DZ), mostly children and adolescents. The study showed a greater similarity between MZ compa...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00295604
更新日期:1982-01-01 00:00:00
abstract::The alphafetoprotein (AFP) concentration in maternal serum was determined before and after chorionic villus sampling (CVS). A significant increase of 20% or more in the pre-CVS level was noted immediately after sampling in 59% of 837 pregnancies indicating some degree of feto-maternal haemorrhage. The increase in the ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291241
更新日期:1988-01-01 00:00:00
abstract::A segregation analysis on 135 Duchenne families from Venetia (Italy) suggests that the proportion of sporadic cases might be less than expected. Support for this view is also given by an analysis of a pooled sample including 284 additional sibships from comparable studies published previously. Several hypotheses were ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291351
更新日期:1984-01-01 00:00:00
abstract::A woman with a balanced translocation t(3;11)(p27;q23) has had three abnormal children. The first child died in infancy, and of the two survivors who show segregation of the derivative maternal translocated chromosomes, one exhibits partial trisomy 11q and the other partial monosomy 11q. The two cases are compared wit...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284603
更新日期:1979-11-01 00:00:00
abstract::Complex investigation of a spontaneous abortus with monosomy 21 was carried out. Phenotypic expression at the organism and tissue level was characterized by the pathology of the external form of the embryo and by abnormalities of the embryonic facial structures, the stomodeum, the anterior part of the primary gut, and...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00527395
更新日期:1977-09-22 00:00:00
abstract::In an attempt to investigate beta-globin gene polymorphism in the Saudi population, DNA samples were analysed using restriction endonucleases, Mst II and Hpa I. Both beta A and beta S genes showed extensive polymorphism and were found to be linked to 13.0 kb, 7.6 kb, 7.0 kb, and 5.6 kb Hpa I fragments. Three DNA sampl...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00282555
更新日期:1986-11-01 00:00:00
abstract::To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 yea...
journal_title:Human genetics
pub_type: 杂志文章,meta分析
doi:10.1007/s00439-014-1500-y
更新日期:2015-02-01 00:00:00
abstract::Hypohaptoglobinaemia and ahaptoglobinaemia occurred in three generations, mainly to male members of a family. Also small amounts of haptoglobin were detected in most of the female relatives. Haemolytic anaemia seemed likely and the glucose 6 phosphate dehydrogenase (G.6.P.D.) activity was normal. The probable genotype...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00294926
更新日期:1981-01-01 00:00:00
abstract::A girl with 46, XX, del (11) (q23), inv (9) (p13, q13) is described. The patient shows many dysplastic signs mainly of the face and skull. The pericentric inversion of chromosome 9 has been inherited from the mother (46, XX, inv (9) (p13, q13)). ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00390443
更新日期:1977-04-07 00:00:00
abstract::Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here a systematic mutational screening of the mitochondrial 12S rRNA gene in 128 Chinese pediatric subjects with sporadic aminoglycoside-induced and non-syndromic hearing loss. We show that aminoglycoside...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-005-1276-1
更新日期:2005-06-01 00:00:00
abstract::We have studied the effects of cocultivation on the frequency of mitomycin C (MMC)-induced chromosomal aberrations. This was carried out by cocultivating Fanconi anemia (FA) cells from the genetic complementation groups A and B with both normal mouse lymphoma L5178Y cells and the derived "FA-like" mutant cells, MCN-15...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00210801
更新日期:1990-05-01 00:00:00
abstract::An 8-month-old female child with the 9p- karyotype: 46,XX,del(9) (p22) is presented, being the first case from among Oriental people. She has many clinical features similar to those described in Caucasian cases. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00295813
更新日期:1977-08-31 00:00:00
abstract::PIG-A, the gene encoding the glycoinositol phospholipid anchor synthetic element that is defective in paroxysmal nocturnal hemoglobinuria (PNH), resides on the X chromosome. In the course of analyses of PIG-A genetic alterations in PNH patients, polymerase chain reaction (PCR) amplification of reverse-transcribed RNA ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00209489
更新日期:1995-06-01 00:00:00
abstract::The development of next-generation sequencing technologies has opened-up some new possibilities to explore the contribution of genetic variants to human diseases and in particular that of rare variants. Statistical methods have been developed to test for association with rare variants that require the definition of te...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-020-02190-y
更新日期:2020-11-01 00:00:00
abstract::Translocation t(11;22)(q23;q11) is the most common constitutional reciprocal translocation in man. Balanced carriers are phenotypically normal, except for decreased fertility, an increased spontaneous abortion rate and a possible predisposition to breast cancer in some families. Here, we report the high resolution map...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000287
更新日期:2000-05-01 00:00:00
abstract::The Great Lakes lie within a region of East Africa with very high human genetic diversity, home of many ethno-linguistic groups usually assumed to be the product of a small number of major dispersals. However, our knowledge of these dispersals relies primarily on the inferences of historical, linguistics and oral trad...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-015-1583-0
更新日期:2015-09-01 00:00:00
abstract::X chromosome inactivation results in dosage equivalency for X-linked gene expression between males and females. However, some X-linked genes show variable X inactivation, being expressed from the inactive X in some females but subject to inactivation in other women. The human tissue inhibitor of metalloproteinases-1 (...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-002-0676-8
更新日期:2002-03-01 00:00:00
abstract::We report clinical and molecular findings in 15 Japanese mosaic females with r(X) chromosomes, 45,X/46,X,r(X), confirmed by fluorescence in situ hybridization (FISH) analysis for DXZ1 and whole X chromosome painting. Cases 1-3, 5-7, and 11-13 had mental retardation (MR), the remaining cases being free from MR. FISH an...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000377
更新日期:2000-11-01 00:00:00
abstract::Five patients with hereditary elliptocytosis (HE) from two unrelated black families were studied. The patients had prominent elliptocytosis and a decreased erythrocyte resistance to heat treatment. In one infant blood smears showed elliptocytosis and poikilocytosis; his erythrocytes fagmented at a lower temperature th...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00388462
更新日期:1985-01-01 00:00:00
abstract::Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic r...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-013-1407-z
更新日期:2014-06-01 00:00:00
abstract::Oocyte loss has a significant impact on fertility and somatic health. Yet, we know little about factors that impact this process. We sought to identify genetic variants associated with ovarian reserve (oocyte number as measured by antral follicle count, AFC). Based on recently published genome-wide scans that identifi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-012-1184-0
更新日期:2012-11-01 00:00:00
abstract::A novel complex mutation consisting of a small deletion/insertion (3958del5ins4) was found in the breast cancer-1 gene (BRCA-1) in three unrelated French breast and/or ovarian cancer families. These mutations occurred at the same nucleotide position of the 3' end of exon 11. The wild-type sequence, CTCAG, was deleted ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050826
更新日期:1998-09-01 00:00:00
abstract::To understand the effects of the interaction between genetic polymorphisms and obesity on the risk of hypertriglyceridemia (HTG), two polymorphisms, an SstI polymorphism on the apolipoprotein CIII gene and a HindIII polymorphism on the lipoprotein lipase gene, were analyzed in 339 Chinese subjects with (82 cases in th...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050511
更新日期:1997-09-01 00:00:00
abstract::We recently observed a significantly increased risk for lung cancer in carriers of p53 germline mutations. Because cigarette smoking is known to play an important role in increasing the risk for lung cancer in the general population, we wanted to determine the role of cigarette smoking in lung cancer risk in people wi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-003-0968-7
更新日期:2003-08-01 00:00:00
abstract::Seven nucleotide sequence polymorphisms were detected within exons of the low-density lipoprotein (LDL) receptor gene using single-strand conformation polymorphism (SSCP) analysis followed by direct sequence analysis on amplified DNA. Four nucleotide changes at nucleotide positions 1617, 1725, 2232, and 2635 were new ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00216148
更新日期:1993-08-01 00:00:00
abstract::Basal levels of C-reactive protein (CRP) have been associated with disease, particularly future cardiovascular events. Twin studies estimate 50% CRP heritability, so the identification of genetic variants influencing CRP expression is important. Existing studies in populations of European ancestry have identified nume...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-008-0517-5
更新日期:2008-07-01 00:00:00
abstract::A population study of Gd- allele distribution was made in similar (age-sex) samples of schoolchildren and students from different ethnic groups: Russians, Ashkenazi Jews, and Azerbaijanians. Both the frequency and the spectrum of the Gd- alleles were quite different. The Gd- frequency in Russians (Kostroma region) was...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00281070
更新日期:1987-03-01 00:00:00
abstract::Rearrangement of the breakpoint cluster region (bcr) and the chromosomal location of c-abl and 3'-bcr were studied in two patients with Philadelphia chromosome (Ph1)-negative chronic myelocytic leukemia (CML). One patient (patient 1) had a normal karyotype and the other (patient 2), 46,XY,inv(3)(q21q26). Both patients...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00286701
更新日期:1989-09-01 00:00:00