What is NUBPL?

Gene Name: NUBPL, acronym for Nucleotide-binding protein-like

Also Known As:  Iron-sulfur protein required for NADH dehydrogenase or IND1

Location: Chromosome 14q12

Symbols: NUBPL; IND1; huInd1; C14orf127

Genetic Inheritance: Recessive

Gene Function: It is an iron-sulfur (Fe/S) protein that, in humans, is encoded by the NUBPL gene. It that has an early role in the assembly of the mitochondrial complex I assembly pathway.

Mutations in the NUBPL gene may cause a rare form of mitochondrial complex I disorder.

Typical clinical signs and symptoms:

  • Age of onset 1-2 years old
  • Developmental delay: Some patients
  • Delay: Motor; Unable to walk
  • Speech: Abnormal (Dysarthria)
  • Eyes: Strabismus; Nystagmus
  • Ataxia: Trunk & Limbs
  • Contractures
  • Spasticity
  • Cognitive: Normal or Reduced
  • Myopathy
  • Other organs: Normal
  • Course: Progressive, continuous or episodic

Laboratory signs:

  • MRI: Leukoencephalopathy with abnormal:
    • Cerebellar cortex: Progressive
    • Cerebral white matter, deep: May resolve
    • Corpus callosum: May resolve
      *Although these are characteristic MRI findings, there are others including abnormalities in the grey matter of the cerebellum, as is discussed in Hope for Katherine Belle.
  • Lactate: Serum normal or high; CSF normal or high
  • NUBPL protein: Reduced
  • Muscle biopsy
    • Histology: Ragged red fibers; No COX- fibers

Biochemistry: Complex I deficiency

Overview of NUBPL Mutations
GeneDx (USA): c.166G>A (maternal); c.815-27T>A (maternal); and c.693+1G>A (paternal)

Ambry 1 & 2 (USA): c.311T>C (maternal); p.L104P (maternal); and c.815-27T>C (paternal)

Kevelam 1 (Arg.): c.166G>A (unknown); and c.815-27T>C (unknown) (older results)

Kevelam 2 (Ger.): c.166G>A (paternal); c.815-27T>C (paternal); and c.667_668insCCTTGTGCTG (maternal)

Kevelam 3&4 (Can.): c.166G>A (paternal); c.815-27T>C (paternal); and c.313G>T (maternal)

Kevelam 5 (USA): c.166G>A (paternal); c.815-27T>A (paternal); and c.693+1G>A (maternal)

Kevelam 6 (Neth.): c.166G>A (maternal); c.815-27T>C (maternal); and c.579A>C (paternal)

Kevelam 7 (Australia): c.166G>A (paternal); c.815-27T>C (paternal); 240-kb deletion (maternal); and 137-kb duplication (maternal)

Research

Sheftel, A. “Human Ind1, an Iron-Sulfur Cluster Assembly Factor for Respiratory Complex I”. Mcb.asm.org. Retrieved 25 April 2015

Sheftel, A. “Human ind1, an iron-sulfur cluster assembly factor for respiratory complex I”. Mol. Cell. Biol. 29 (22): 6059–6073. PMID 19752196.

Calvo, S. “High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency”. PMID 20818383.

Kevelam, S. “NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern”. Neurology 80 (17): 1577–1583. PMID 23553477

NUBPL Families In the Press

Connect

The more we connect with other NUBPL families, the closer we get to finding a cure.  Do you have NUBPL or do you think you may?  Or, are you a researcher who is interested in studying NUBPL?  Please contact us.  We want to hear from you. Although some families are public about their journey, we respect your desire for privacy.

Katherine Belle’s Story, Age 3
Katherine’s whole exome sequencing results identified the following:

Compound heterozygous for the c.693+1G>A mutation and the c.815-27T>C;c.166G>A likely-disease causing complex allele in the NUBPL gene.  This is associated with mitochondrial complex 1 deficiency.
IMG_781510338714_10204199751976992_1569947081705208359_nIMG_5461

Cali and Ryaan’s Story, Ages 16 and 6
IMG_6805 IMG_6804IMG_6809valentine day special stars family portrait

FULL VIDEO – The Spooner Family Documentary: The Life We Live http://thelifewelivedoc.com

Contact

NUBPL.org is a patient-run web site created for parents, doctors, or researchers who may know individuals with NUBPL. The more patients, the greater our sense of community, resources, and research opportunities to find a cure. Contact: gcmccoy1@aol.com or NUBPL.org.

Donate
Hope for Katherine Belle

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