PMID- 23749988
OWN - NLM
STAT- MEDLINE
DCOM- 20140218
LR  - 20220316
IS  - 1468-6244 (Electronic)
IS  - 0022-2593 (Linking)
VI  - 50
IP  - 8
DP  - 2013 Aug
TI  - Recessive truncating NALCN mutation in infantile neuroaxonal dystrophy with 
      facial dysmorphism.
PG  - 515-20
LID - 10.1136/jmedgenet-2013-101634 [doi]
AB  - BACKGROUND: Infantile neuroaxonal dystrophy (INAD) is a recessive disease that 
      results in total neurological degeneration and death in childhood. PLA2G6 
      mutation is the underlying genetic defect, but rare genetic heterogeneity has 
      been demonstrated. One of the five families we studied did not link to PLA2G6 
      locus, and in the family one of the two affected siblings additionally had 
      atypical features including facial dysmorphism, pectus carinatum, scoliosis, pes 
      varus, zygodactyly and bilateral cryptorchidism as well as cerebellar atrophy, as 
      previously reported. METHODS: Sural biopsy was investigated by electron 
      microscopy. PLA2G6 was screened for mutations by Sanger sequencing. In the 
      mutation-free family, candidate disease loci were found via linkage analysis 
      using data from single nucleotide polymorphism genome scans. Exome sequencing was 
      applied to find the variants at the loci. RESULTS: PLA2G6 mutations were 
      identified in four families including the one with an unusually severe phenotype 
      that led to death within the first 2 years of life. In the remaining family, 
      seven candidate loci totalling 15.2 Mb were found and a homozygous truncating 
      mutation p.Q642X was identified in NALCN at 13q32.3. The patients are around 
      20-years-old. CONCLUSIONS: NALCN is the gene responsible for INAD with facial 
      dysmorphism. The patients have lived to adulthood despite severe growth and 
      neuromotor retardation. NALCN forms a voltage-independent ion channel with a role 
      in the regulation of neuronal excitability. Our findings broaden the spectrum of 
      genes associated with neuroaxonal dystrophy. Testing infants with idiopathic 
      severe growth retardation and neurodegeneration for NALCN mutations could benefit 
      families.
FAU - Koroglu, Cigdem
AU  - Koroglu C
AD  - Department of Molecular Biology and Genetics, Bogazici University, Istanbul, 
      Turkey.
FAU - Seven, Mehmet
AU  - Seven M
FAU - Tolun, Aslihan
AU  - Tolun A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130607
PL  - England
TA  - J Med Genet
JT  - Journal of medical genetics
JID - 2985087R
RN  - 0 (Ion Channels)
RN  - 0 (Membrane Proteins)
RN  - 0 (NALCN protein, human)
RN  - 0 (Sodium Channels)
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Face/*abnormalities
MH  - Female
MH  - Humans
MH  - Infant
MH  - Ion Channels
MH  - Male
MH  - Membrane Proteins
MH  - Mutation
MH  - Neuroaxonal Dystrophies/*genetics/pathology
MH  - Phenotype
MH  - Sodium Channels/*genetics
OTO - NOTNLM
OT  - Genetics
OT  - Linkage
OT  - Neurology
EDAT- 2013/06/12 06:00
MHDA- 2014/02/19 06:00
CRDT- 2013/06/11 06:00
PHST- 2013/06/11 06:00 [entrez]
PHST- 2013/06/12 06:00 [pubmed]
PHST- 2014/02/19 06:00 [medline]
AID - jmedgenet-2013-101634 [pii]
AID - 10.1136/jmedgenet-2013-101634 [doi]
PST - ppublish
SO  - J Med Genet. 2013 Aug;50(8):515-20. doi: 10.1136/jmedgenet-2013-101634. Epub 2013 
      Jun 7.