Abstract:
:Cobalamin (cbl) C disease is a rare autosomal recessive inheritance disease, which is the most common cobalamin metabolic disorder. Its clinical phenotype involves multiple systems with varying degrees of severity, where in mild cases can be asymptomatic for many years, whereas severe cases may cause death during the neonatal period. The disease is caused by mutations in the MMACHC gene located on chromosome 1p34.1 that contains 5 exons; among which, exons 1-4 have an 849 bp coding sequence that encodes a protein containing 282 amino acids. Through clinical physical examination and laboratory tests, especially blood and urine screening, we found 28 cblC pediatric patients with clinical manifestations, such as mental retardation, motor development delay, epilepsy, metabolic acidosis, vomiting and diarrhea. By Sanger sequencing, we found homozygous or compound heterozygous mutations of MMACHC in 27 of the patients, and single heterozygous mutation of MMACHC in one of them. The c.609G > A, c.658-660delAAG, c.80A > G and c.482G > A mutations accounted for 43.64% (24/55), 10.91% (6/55), 9.09% (5/55) and 7.27% (4/55) of all the mutations, respectively. This spectrum finding is basically consistent with the previously reported data in Chinese patients. The most common c.609G > A mutation may likely lead to early-onset cblC disease. In previous literature involving a large sample of Caucasian cblC cases, the mutation spectrum of MMACHC gene is almost completely different from that of the Chinese population. The most common mutations in the Caucasian population were c.271dupA, c.394C > T and c.331C > T, which account for 48.05% (542/1128), 13.65% (154/1128) and 7.36% (83/1128) of all the mutant alleles, respectively. The c.271dupA mutation and c.331C > T mutation were mainly associated with early-onset cblC in children less than 1 year old, whilst the c.394C > T mutation was mainly associated with late-onset cblC patients characterised by isolated acute nervous system abnormalities. We also analysed the cause behind the different mutation spectrum of MMACHC gene between the Chinese and Caucasian populations.
journal_name
Eur J Med Genetjournal_title
European journal of medical geneticsauthors
Wang C,Li D,Cai F,Zhang X,Xu X,Liu X,Zhang C,Wang D,Liu X,Lin S,Zhang Y,Shu Jdoi
10.1016/j.ejmg.2019.103713subject
Has Abstractpub_date
2019-10-01 00:00:00pages
103713issue
10eissn
1769-7212issn
1878-0849pii
S1769-7212(18)30946-7journal_volume
62pub_type
杂志文章,评审abstract::Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions characterized by delays in social interactions and communication as well as displays of restrictive/repetitive interests. DNA copy number variants have been identified as a genomic susceptibility factor in ASDs and imply significant genetic hete...
journal_title:European journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1016/j.ejmg.2013.05.006
更新日期:2013-08-01 00:00:00
abstract::Congenital diarrhea and enteropathies (CODEs) are a group of monogenic disorders that often present with severe diarrhea in the first weeks of life. Enteric anendocrinosis (EA), an extremely rare cause of CODE, is characterized by a marked reduction of intestinal enteroendocrine cells (EC). EA is associated with reces...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2020.103981
更新日期:2020-09-01 00:00:00
abstract::A very recent study suggested that HCN4 mutations could be associated with sinusal bradycardia and myocardial non compaction. A French family with 3 affected sisters presenting the same clinical phenotype (sinus bradycardia in combination with non compaction cardiomyopathy (NCCM)) have benefited both from a systematic...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2015.06.004
更新日期:2015-09-01 00:00:00
abstract::We report on an 8(1)/(2)-year-old girl with severe pre- and postnatal growth retardation, congenital heart malformation, facial asymmetry, oculocutaneous albinism without misrouting and subluxation of the radial heads. Her intelligence was in the low normal range. By GTG-banding a deletion of band 15q26 was found. Arr...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2007.08.003
更新日期:2007-11-01 00:00:00
abstract::Baraitser-Winter syndrome was first described as a syndrome of iris coloboma, ptosis, hypertelorism, and mental retardation (Baraitser and Winter 1988; Baraitser, 2016). The phenotypic spectrum has since broadened to include other facial dysmorphic features, deafness, microcephaly, lissencephaly, and CNS findings (Bar...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2017.10.006
更新日期:2018-01-01 00:00:00
abstract::Split hand/foot malformation (SHFM) or ectrodactyly is a rare congenital disorder affecting limb development characterized by clinical and genetic heterogeneity. SHFM is usually inherited as an autosomal dominant trait with incomplete penetrance. Isolated and syndromic forms are described. The extent of associated mal...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2019.103805
更新日期:2020-04-01 00:00:00
abstract::Axenfeld-Rieger syndrome (ARS) is a heterogeneous clinical entity transmitted in an autosomal dominant manner. The main feature, Axenfeld-Rieger Anomaly (ARA), is a malformation of the anterior segment of the eye that can lead to glaucoma and impair vision. Extra-ocular defects have also been reported. Point mutations...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2017.10.018
更新日期:2018-02-01 00:00:00
abstract::The EEF1A2 gene encodes eukaryotic translation elongation factor 1α2, an integral component of the elongation factor complex. Heterozygous pathogenic variants in EEF1A2 are associated with neurodevelopmental disorders characterized by epilepsy, global developmental delay, and autism. To date, dilated cardiomyopathy ha...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2020.104121
更新日期:2021-01-01 00:00:00
abstract::In addition to Down syndrome, individuals with other constitutional abnormalities of chromosome 21 have an increased risk of developing childhood acute lymphoblastic leukaemia (ALL). Specifically, carriers of the Robertsonian translocation between chromosomes 15 and 21, rob(15;21) (q10; q10)c, have ∼2,700 increased ri...
journal_title:European journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1016/j.ejmg.2016.01.006
更新日期:2016-03-01 00:00:00
abstract:INTRODUCTION:Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder due to heterozygous pathogenic variants in transforming growth factor beta (TGFβ) signaling-related genes. LDS types 1-6 are distinguished depending on the involved gene. LDS is characterized by multiple arterial aneurysms and d...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2019.103727
更新日期:2019-10-01 00:00:00
abstract::Recently a mutation in the SNX10 gene that belongs to the sorting nexin family was identified as a cause of a new subset of human autosomal recessive osteopetrosis. Here, we identified a novel homozygous mutation (c.46C > T, p.Arg16X) in SNX10, in an Iraqi boy from a consanguineous family with a history of infantile o...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2012.10.010
更新日期:2013-01-01 00:00:00
abstract::Apparently balanced chromosome abnormalities are occasionally associated with mental retardation (MR). These balanced rearrangements may disrupt genes. However, the phenotype may also be caused by small abnormalities present at the breakpoints or elsewhere in the genome. Conventional karyotyping is not instrumental fo...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2010.06.003
更新日期:2010-09-01 00:00:00
abstract::X-linked chronic granulomatous disease is a primary immunodeficiency caused by mutations in CYBB. Although large deletions involving CYBB are known to cause contiguous gene syndrome (CGS), only a few patients have been studied precisely at the molecular levels. Our study determined the deletion breakpoints in two pati...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2010.08.003
更新日期:2010-11-01 00:00:00
abstract::Microphthalmia with limb anomalies (MLA, OMIM, 206920) is a rare autosomal-recessive disease caused by biallelic pathogenic variants in the SMOC1 gene. It is characterized by ocular disorders (microphtalmia or anophtalmia) and limb anomalies (oligodactyly, syndactyly, and synostosis of the 4th and 5th metacarpals), va...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2018.11.012
更新日期:2019-11-01 00:00:00
abstract::Only a few subjects carrying supernumerary marker chromosomes derived from 19 chromosome (sSMC(19)) have been described to date and for a small portion of them the genic content has been defined at the molecular level. We present seven new different sSMCs(19) identified in eight individuals, seven of whom unrelated. T...
journal_title:European journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1016/j.ejmg.2017.11.007
更新日期:2018-03-01 00:00:00
abstract::We report a child with a 785kb deletion of the 3p14.1p13 region including the genes FOXP1, EIF4E3, PROK2, GPR27 resulting in speech delay, contractures, hypertonia and blepharophimosis. FOXP1 and FOXP2 are transcription factors containing a polyglutamine tract and a forkhead DNA binding domain. They both play a role i...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2009.03.012
更新日期:2009-03-01 00:00:00
abstract::We report on the observation of an interstitial deletion of the long arm of chromosome 1 diagnosed prenatally in a 28 weeks gestation fetus by standard karyotype. Amniocentesis was performed because of an increased Down syndrome maternal serum screening and ultrasonographic abnormalities. Fetus autopsy showed an intra...
journal_title:European journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1016/j.ejmg.2006.03.004
更新日期:2006-11-01 00:00:00
abstract::Synpolydactyly (SPD) is an autosomal dominant limb malformation caused by mutations in the gene HOXD13. We investigated a Chinese family in which three individuals across three generations were affected with distinctive limb malformations. We extracted genomic DNA from the affected and three unaffected individuals fro...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2010.10.007
更新日期:2011-03-01 00:00:00
abstract::We report the clinical and neuroradiological findings in a young boy harboring the 9p deletion syndrome including the novel findings of thalamic infarction and germinal matrix haemorrhage and neonatal hyperinsulinemic hypoglycemia. Both the hypoglycemic events and the ventriculomegaly found in this patient have previo...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2018.03.009
更新日期:2018-08-01 00:00:00
abstract::Multiple sclerosis is not known to be a risk factor for subsequent development of cancer. Recently, a multiple sclerosis locus was mapped adjacent to BRCA1 gene. We present a familial case affected by multiple sclerosis and cancer. We identified a c.5266dupC (5382insC) frameshift mutation in a 33-year-old woman with b...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2013.07.006
更新日期:2013-10-01 00:00:00
abstract::We identified a 495 Kb interstitial deletion of chromosome Xp22.2, centered on the AP1S2 gene, by means of oligonucleotide array comparative genomic hybridisation (array-CGH) in a child with marked hypotonia in the first months of life, psychomotor retardation, severely delayed walking and speech development, and unsp...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2011.12.001
更新日期:2012-02-01 00:00:00
abstract:PURPOSE:To investigate whether increased parental age is associated with an increased risk for de novo copy number variant (CNV) formation in offspring. METHODS:CNV calls from 2323 individuals referred to Signature Genomic Laboratories for clinical microarray-based comparative genomic hybridization were investigated; ...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2019.103829
更新日期:2020-04-01 00:00:00
abstract::CHARGE syndrome (MIM#214800) (Coloboma, Heart defect, Atresia of choanae, Retarded growth and development, Genital hypoplasia, Ear abnormalities/deafness) is caused by heterozygous mutation of CHD7 transmitted in an autosomal dominant manner. In this report, we describe a patient with bilateral hearing impairment, unu...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2016.02.012
更新日期:2016-04-01 00:00:00
abstract::In a genetically isolated community in the Netherlands four severe recessive genetic disorders occur at relatively high frequency (pontocerebellar hypoplasia type 2 (PCH2), fetal akinesia deformation sequence (FADS), rhizomelic chondrodysplasia punctata type 1 (RCDP1), and osteogenesis imperfecta (OI) type IIB/III. Ov...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2015.01.004
更新日期:2015-03-01 00:00:00
abstract::Some cases of chromosome 7p22.3 deletions have been reported, but the genotype-phenotype correlation is still uncertain. Neurodevelopmental delay and heart anomalies have been recorded as the most recurrent defects. We describe the clinical features of a four-year-old male child with a 139 kb deletion at 7p22.3 involv...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2019.103772
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2019.103767
更新日期:2020-03-01 00:00:00
abstract::Here we report three patients affected with neurodevelopmental disorders and harbouring 21q21 deletions involving NCAM2 gene. NCAM (Neural Cell Adhesion Molecule) proteins are involved in axonal migration, synaptic formation and plasticity. Poor axonal growth and fasciculation is observed in animal models deficient fo...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2014.11.004
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Fetal chromosome aberrations and sub-chromosomal copy number variations (CNVs) are not rare. There are several ways to detect duplications and deletions; cell-free DNA screening (cfDNA screening) is nowadays an accurate and safe detection method. The objective of this study is to report the feasibility of cf...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2018.06.012
更新日期:2019-02-01 00:00:00
abstract::Alexander disease (AxD), a fatal degenerative leukoencephalopathy, is caused by de novo heterozygous missense mutations in the Glial Fibrillary Acidic Protein (GFAP) gene. The pathological hallmark of the disease is the presence of Rosenthal fibers, cytoplasmic inclusions in astrocytes, composed mainly of GFAP, αB-cry...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2015.07.002
更新日期:2015-09-01 00:00:00
abstract:PURPOSE:Considering the paucity of reports on large series of patients with tibial hemimelia, we assessed the clinical spectrum of this rare congenital disorder in patients seen at a single Indian center over 10 years. METHODS:Retrospective review of medical records of patients seen at single center in 10 years. RESU...
journal_title:European journal of medical genetics
pub_type: 杂志文章
doi:10.1016/j.ejmg.2019.05.005
更新日期:2019-07-01 00:00:00