Abstract:
BACKGROUND:Hypertrophic cardiomyopathy (HCM) is frequently fatal in infancy. Mitochondrial disease causing infantile HCM is characterised by extreme biochemical and genetic heterogeneity, but deficiency of respiratory chain complex I is observed relatively frequently. Identification of the precise genetic basis has prognostic implications for the likelihood of neurological involvement. OBJECTIVE:The authors' objective is to report two heterozygous missense mutations in the NDUFAF1 gene as a cause of fatal infantile HCM in a patient with isolated complex I deficiency. METHODS:The authors investigated a cohort of 30 paediatric patients with complex I deficiency using biochemical and genetic approaches. The patients were clinically heterogeneous; phenotypes included HCM, Leigh syndrome, other encephalomyopathies and multisystem disease. Complex I assembly was evaluated using Blue Native polyacrylamide gel electrophoresis. RESULTS:Sequence analysis of NDUFAF1 revealed compound heterozygous missense mutations (c.631C>T;p.Arg211Cys and c.733G>A;p.Gly245Arg) in one patient with fatal infantile HCM. These changes were absent in 240 ethnically matched control alleles. No NDUFAF1 mutations were observed in the remaining patients. Functional studies demonstrated a severe reduction in NDUFAF1 protein in Western blots of patient fibroblasts and accumulation of abnormal complex I assembly intermediates on Blue Native polyacrylamide gel electrophoresis. CONCLUSIONS:The authors report a case of fatal infantile HCM caused by missense mutations in NDUFAF1 associated with complex I misassembly. Establishing a genetic diagnosis in mitochondrial cardiomyopathy is challenging and achieved in only a minority of cases because of complex genetics. A precise genetic diagnosis is important to provide accurate prognostic and genetic counselling advice regarding recurrence risks and to guide future reproductive options.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Fassone E,Taanman JW,Hargreaves IP,Sebire NJ,Cleary MA,Burch M,Rahman Sdoi
10.1136/jmedgenet-2011-100340subject
Has Abstractpub_date
2011-10-01 00:00:00pages
691-7issue
10eissn
0022-2593issn
1468-6244pii
jmedgenet-2011-100340journal_volume
48pub_type
杂志文章abstract:BACKGROUND:A limited number of studies aimed at investigating the possible association of Y-chromosome haplogroups with microdeletions of the azoospermia factors (AZFs) or with particular infertile phenotypes, but definitive conclusions have not been attained. The main confounding elements in these association studies ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2006.046433
更新日期:2007-03-01 00:00:00
abstract::Four studies reported an increasing incidence of pyloric stenosis during the late 1970s from geographically diverse areas of the United Kingdom. It was suggested that the increased incidence might be related to changes in infant feeding practices. We used data from the Metropolitan Atlanta Congenital Defects Program, ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.24.8.482
更新日期:1987-08-01 00:00:00
abstract::We report three sisters and their father with a reciprocal balanced translocation, rcp t(8;11)(q24.3;p15.1) and the same abnormal phenotypes, including mental retardation, growth disturbance, and amblyopia. It is considered that the abnormal phenotypes in our four cases might result from a tiny deletion or gene mutati...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.26.10.642
更新日期:1989-10-01 00:00:00
abstract:BACKGROUND:Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of non-chromosomal HPE. The severity spectrum is wide, ranging from incompatibility ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:2012-07-01 00:00:00
abstract::Since the advent of C-banding as a routine diagnostic procedure, the significance of heterochromatic polymorphism has been questioned. Some workers have considered variations in heterochromatin in chromosomes 1 and 9 to be associated with fetal wastage, recurrent abortions, and abnormal phenotypes. Over a 15-month per...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.16.5.358
更新日期:1979-10-01 00:00:00
abstract::Costovertebral dysplasia comprises multiple malformations of the vertebrae and ribs, with a characteristic clinical picture of short trunk dwarfism, short neck, scoliosis, and rib cage deformity. We describe two sibs with the syndrome who are presumed to represent the autosomal recessive form of the disorder. One sib ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.20.6.441
更新日期:1983-12-01 00:00:00
abstract::We describe a patient with the unusual association of cleft palate, bilateral choanal atresia, curly hair, and congenital hypothyroidism. This association has been reported before in two brothers and may represent a new syndrome. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
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更新日期:1993-05-01 00:00:00
abstract::A study of mutation, biological fitness, and patterns of family building in Huntington's chorea has been carried out, based on a previously reported population study of the disorder in South Wales. No unequivocal new mutation was identified among 101 kindreds containing 418 affected persons, which supports the extreme...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.20.1.12
更新日期:1983-02-01 00:00:00
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journal_title:Journal of medical genetics
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更新日期:1977-08-01 00:00:00
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更新日期:1990-03-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:2012-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1136/jmg.25.4.222
更新日期:1988-04-01 00:00:00
abstract::World wide data on presymptomatic testing for Huntington's disease using closely linked DNA markers show that 1479 persons at risk received completed test results up to the end of 1991. Testing has been carried out in 19 countries, with at least 88 centres involved, and numbers have levelled off after a peak in 1990. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:1993-12-01 00:00:00
abstract::This paper describes a genetically male infant with impaired male sex development and partial 9p monosomy. The external genitalia were ambiguous with microphallus (penile length at birth 10 mm, mean age matched normal length 29 mm (SD 5)), hypospadias, and hypoplastic scrotum. The tests were undescended and severely h...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.34.4.331
更新日期:1997-04-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:2021-01-01 00:00:00
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journal_title:Journal of medical genetics
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pub_type: 信件
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pub_type: 杂志文章
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