Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Functional Assessment of Variants Associated with Wolfram Syndrome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. PAICS deficiency, a new defect of de novo purine synthesis resulting in multiple congenital anomalies and fatal outcome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Danish expanded newborn screening is a successful preventive public health programme

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. The impact of consanguinity on the frequency of inborn errors of metabolism

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Exome sequencing for syndrome diagnostics

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Arvelige neurometaboliske sygdomme

    Publikation: Bidrag til bog/antologi/rapportBidrag til bog/antologiUndervisning

  • Anita M Quintana
  • Hung-Chun Yu
  • Alison Brebner
  • Mihaela Pupavac
  • Elizabeth A Geiger
  • Abigail Watson
  • Victoria L Castro
  • Warren Cheung
  • Shu-Huang Chen
  • David Watkins
  • Tomi Pastinen
  • Flemming Skovby
  • Bruce Appel
  • David S Rosenblatt
  • Tamim H Shaikh
Vis graf over relationer

CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant, c.240C > G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo demonstrated that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role for HCFC1 in vertebrate craniofacial development. High throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development.

OriginalsprogEngelsk
TidsskriftHuman Molecular Genetics
Vol/bind26
Udgave nummer15
Sider (fra-til)2838-2849
Antal sider12
ISSN0964-6906
DOI
StatusUdgivet - 1 aug. 2017

ID: 52804175