A novel missense mutation in
EDA gene underlies X-linked
non-syndromic hypodontia
Muhammad Ayub
Asst.Professor in Biochemistry
University of Balochistan Quetta
Causes of Human Genetic
Disorders
• Consanguineous Marriage
• Social Custom
• Lack of Awareness
Syndromic and non-syndromic
teeth anomalies
• Hypodontia
• Oligodontia
• Anodontia
Mode of Inheritance
• Autosomal dominant
• Autosomal recessive
• X-linked recessive
Genes in tooth agenesis
• PAX9, MSX1, AXIN2 are already known
for autosomal dominant/recessive tooth
abnormalities
• EDA is known for X-linked recessive nonsyndromic hypodontia
Methods
• Pedigree
• Blood sampling
– EDTA Vacutainer
• Genomic DNA extraction
– Phenol-chloroform method
• Polymerase chain reaction
– Genotyping
– DNA sequencing
Pedigree
I
I-1
I-2
II
II-1
II-3
II-2
II-4
III
III-1
III-2
III-4
III-3
•
IV
IV-1
IV-2
IV-3
IV-4
IV-5
IV-6
V
V-1
V-2
Clinical Features
Methods
• Blood sampling
– EDTA Vacutainer
• Genomic DNA extraction
– Phenol-chloroform method
• Polymerase chain reaction
– Genotyping
– DNA sequencing
Methods
• Genotyping of five generations Pakistani
family with X-linked isolated hypodontia
was ascertained
• Linkage through microsatellite markers
was established on Xq12-q13.1
• DNA sequence analysis (ABI 310 Genetic
Analyzer) revealed a novel mutation in
exon 8 (c.993G>C, p.Q331H)
Linkage to Xq12-q13.1
EDA gene sequencing
H
Q/H
Q
Conservation of Q aa at 331in EDA
tumor necrosis factor
EDA gene mutations so far
S.No.
Mutations
Protein effect
Mutation type
Reference
1
Exon-1 c.193C>G
(p.R65G)
Missense
Tao et al. (2006)
2
Exon-8 c.1072C>T
(p.Q358E)
Missense
Tarpey et al. (2007)
3
Exon-9 c.1091T>C
(p.M364T)
Missense
Rasool et al. (2008)
4
Exon-8 c.1013C>T
(p.T338M)
Missense
Han et al. (2008)
5
Exon-1 c.200A>T
(p.E67V)
Missense
Fan et al. (2008)
6
Exon-7 c.758T>C
L253P
Missense
Fan et al. (2008)
7
Exon-9 c.926T>G
V309G
Missense
Fan et al. (2008)
Altered
Splice donor site
Fan et al. (2008)
8
Exon-5 c.IVS5+1G>A
9
Exon-3 c.491A>C
E164A
Missense
Fan et al. (2008)
10
Exon-8 c.1336T>C
(p.V365A)
Missense
Mues et al. (2009)
11
Exon-8 c.993G>C
(p.Q331H)
Missense
Ayub et al. (2009)
(present study)
Ayub M, Rehman FU, Yasinzai M, Ahmad W. A novel
missense mutation in the EDA gene underlies X-linked
recessive non-syndromic hypodontia. Int J Dermatol
(in press) impact factor 1.5
AKNOLEDGMENTS
• Prof. Dr. Masoom Yasinzai Supervisor, Yasinzai,Vice
Chancellor Quaid-i-Azam university islamabad
• Prof. Dr. Wasim Ahmad, Co-supervisor QAU, Islamabad
• Lab fellows
• The Family members who participated in the study
Thank you