A founder ectodysplasin A receptor (EDAR) mutation results in a high frequency of the autosomal recessive form of hypohidrotic ectodermal dysplasia in India.
BACKGROUND
Hypohidrotic/anhidrotic ectodermal dysplasia (HED) is a rare Mendelian disorder affecting ectodermal tissues. The disease is primarily caused by inactivation of any one of three genes, namely ectodysplasin A1 (EDA-A1), which encodes a ligand belonging to the tumour necrosis factor (TNF) superfamily; ectodysplasin A receptor (EDAR), encoding the EDA-A1 receptor and ectodysplasin A receptor-associated death domain (EDARADD), encoding an adaptor protein. X-linked recessive (EDA-A1), the predominant form of HED, as well as autosomal recessive and dominant (EDAR and EDARADD) inheritance patterns have been identified in affected families.


OBJECTIVE
To determine the common genes causing HED in India.


METHODS
We performed mutation analysis on 26 HED families from India (including 30 patients). In addition, we carried out sequence and structural analysis of missense/nonsense and insertion/deletion mutations.


RESULTS
Among the 26 families analysed, disease-causing EDAR mutations were identified in 12 (46%) while EDA-A1 mutations were detected in 11 (42%). Four novel mutations in EDAR and five in EDA-A1 were identified. More importantly, a possible founder EDAR mutation, namely c.1144G>A, was identified in five independent families, thus accounting for about one-fifth of affected families in whom mutation was detected. A majority of EDA-A1 mutations localized to the TNF-like domain while the location of EDAR mutations was more widespread.


CONCLUSIONS
This is the first report of a founder EDAR mutation and of a significantly high frequency of autosomal recessive HED.
Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500001, India. bashyam@cdfd.org.in
M D
MD
Bashyam
A K
AK
Chaudhary
E C
EC
Reddy
V
V
Reddy
V
V
Acharya
H A
HA
Nagarajaram
A R R
AR
Devi
L
L
Bashyam
A B
AB
Dalal
N
N
Gupta
M
M
Kabra
M
M
Agarwal
S R
SR
Phadke
R
R
Tainwala
R
R
Kumar
S V
SV
Hariharan
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D053360:Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive / Q000453:epidemiology / Q000235:genetics*; D005091:Exons; D005260:Female; D018703:Founder Effect; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053338:Receptors, Ectodysplasin / Q000235:genetics*
D053338:Receptors, Ectodysplasin