Is Arg5 in HOXDNA binding domain of HOXB1 hot spot for congenital facial paralysis mimicking Moebius syndrome?

Uyguner Z. O., Özgür H., Altunoğlu U., Toksoy G., Başaran S., Bokhoven H. V., ...Daha Fazla

European Human Genetics Conference 2013, Paris, Fransa, 8 - 11 Haziran 2013, cilt.21, sa.1, ss.98

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 21
  • Basıldığı Şehir: Paris
  • Basıldığı Ülke: Fransa
  • Sayfa Sayıları: ss.98
  • İstanbul Üniversitesi Adresli: Evet

Özet

Congenital facial paralysis (CFP) and Moebius syndrome (MBS; MIM

157900) are highly sporadic, formulating classical gene identi􀏐ication algorithms

dif􀏐icult, assigning candidate gene approach compatible. Mutant

mice for Hoxb1 were long before reported to present features of facial nerve

defects, resembling MBS, only very recently associated with human phenotype.

Currently, homozygous c.619C>T in HOXB1 revealed in the two CFP

affected individuals from two different families, both from the same geographic

origin, altering arginine to cysteine at 207 (p.arg207cys) corresponds

arg5 residue of the HOXB1 homeodomain.

We have screened our cohort of 33 sporadic MBS and CFP patients for mutation

on HOXB1 and identi􀏐ied homozygous c.620G>A in one consanguineous

family. Alteration changes the same neutral-polar arginine, via second nucleotide,

resulting to basic-polar histidine (p.arg207his). Clinical investigation

of our case presented left esotropia, right 􀏐lattened/broad nasal bridge,

external ear defects, high arched palate, bilateral cranial nerve VII dysfunction,

diagnosed as CFP. We further screened HOXB1 in 56 DNA samples of

MBS cases, referred to us from Radbound University Nijmegen-Holland,

none found to carry any pathological alteration. It is surprising that, such a

rare disorder with three only identi􀏐ied mutation striking the same conserved

amino acid, delegating arg5 the achilles of HOXB1 protein. Up to date,

out of 267 families with MBS or with the facial weakness, component of

MBS (177 from Webb et al.2012, 56 from Nijmegan group and 34 from our

center), only three reported to carry mutations in HOXB1 gene, 􀏐iguring the

prevalence of HOXB1 mutation frequency to be 1.12%.