Novel recessive BFSP2 and PITX3 mutations: Insights into mutational
mechanisms from consanguineous populations
Aldahmesh, MA ; Khan, AO [ 2 ]; Mohamed, J ; Alkuraya, FS [ 1,3,4,5 ]
GENETICS IN MEDICINE
Volume: 13, Issue: 11, Pages: 978-981, DOI: 10.1097/GIM.0b013e31822623d5,
Published: NOV 2011, Publisher LIPPINCOTT WILLIAMS & WILKINS, 530 WALNUT ST,
PHILADELPHIA, PA 19106-3621 USA
ISSN: 1098-3600
Abstract
Purpose: Designating mutations as recessive or dominant is a function of the effect of the
mutant allele on the phenotype. Genes in which both classes of mutations are known to
exist are particularly interesting to study because these mutations typically define distinct
pathogenic mechanisms at the molecular level. Methods: We studied two
consanguineous families with different eye phenotypes and used a combination of
candidate gene analysis and homozygosity mapping to identify the underlying genetic
defects. Results: In one family, a novel BFSP2 mutation causes autosomal recessive
diffuse cortical cataract with scattered lens opacities, and in another, a novel PITX3
mutation causes an autosomal recessive severe form of anterior segment dysgenesis
and microphthalmia. Conclusion: We show that BFSP2 and PITX3, hitherto known to
cause eye defects only in a dominant fashion, can also present recessively. The likely null
nature of both mutations and lack of manifestation in heterozygotes strongly argues for a
mechanism other than loss of function in the previously reported dominant mutations in
these two genes. Thus, study of consanguineous populations has the additional
advantage of not only identifying novel recessive genes but also defining the mutational
mechanism of dominant disorders. Genet Med 2011:13(11):978-981.
Keywords
Author Keywords:sclerocornea; recessive mutations; homozygosity; intermediate fibers;
BFSP2; PITX3; juvenile cataract
KeyWords Plus:INTERMEDIATE-FILAMENT CYTOSKELETON; EYE LENS; BEADED
FILAMENT; JUVENILE-ONSET; CATARACT; PROTEIN; FAMILIES; CP49
Author Information
Reprint Address: Alkuraya, FS E-mail Addresses:falkuraya@kfshrc.edu.sa
King Faisal Specialist Hosp & Res Ctr, Dept Genet, Dev Genet Unit, MBC 03,POB 3354,
Riyadh 11211, Saudi Arabia.
Organization-Enhanced Name(s)
King Faisal Specialist Hospital & Research Center
King Faisal Specialist Hospital & Research Center - Riyadh
Addresses:
[ 1 ] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Dev Genet Unit, Riyadh 11211,
Saudi Arabia
Organization-Enhanced Name(s)
King Faisal Specialist Hospital & Research Center
King Faisal Specialist Hospital & Research Center - Riyadh
[ 2 ] King Khalid Eye Specialist Hosp, Dept Pediat Ophthalmol, Riyadh, Saudi Arabia
Organization-Enhanced Name(s)
King Khaled Eye Specialist Hospital
King Khalid University Hospital
King Saud University
[ 3 ] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh, Saudi Arabia
Organization-Enhanced Name(s)
Alfaisal University
[ 4 ] King Khalid Univ Hosp, Dept Pediat, Riyadh 11472, Saudi Arabia
Organization-Enhanced Name(s)
King Khalid University Hospital
King Saud University
[ 5 ] King Saud Univ, Coll Med, Riyadh 11461, Saudi Arabia
Organization-Enhanced Name(s)
King Saud University