Mutation Screening of the HGD Gene Identifies a Novel Alkaptonuria
Mutation with Significant Founder Effect and High Prevalence
By:Sakthivel, S (Sakthivel, Srinivasan)[ 1 ] ; Zatkova, A (Zatkova, Andrea)[ 2 ] ; Nemethova, M (Nemethova,
Martina)[ 2 ] ; Surovy, M (Surovy, Milan)[ 3 ] ;Kadasi, L (Kadasi, Ludevit)[ 2,3 ] ; Saravanan, MP (Saravanan, Madurai P.)[ 4 ]
ANNALS OF HUMAN GENETICS
Volume: 78
Issue: 3
Pages: 155-164
DOI: 10.1111/ahg.12055
Published: MAY 2014
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Abstract
Alkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in the homogentisate 1, 2-dioxygenase
(HGD) gene located on Chromosome 3q13.33. AKU is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000,
but Slovakia and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our study focused on studying
the frequency of AKU and identification of HGD gene mutations in nomads. HGD gene sequencing was used to identify
the mutations in alkaptonurics. For the past four years, from subjects suspected to be clinically affected, we found 16
positive cases among a randomly selected cohort of 41 Indian nomads (Narikuravar) settled in the specific area of Tamil
Nadu, India. HGD gene mutation analysis showed that 11 of these patients carry the same homozygous splicing
mutation c.87 + 1G > A; in five cases, this mutation was found to be heterozygous, while the second AKU-causing
mutation was not identified in these patients. This result indicates that the founder effect and high degree of
consanguineous marriages have contributed to AKU among nomads. Eleven positive samples were homozygous for a
novel mutation c.87 + 1G > A, that abolishes an intron 2 donor splice site and most likely causes skipping of exon 2.
The prevalence of AKU observed earlier seems to be highly increased in people of nomadic origin.
Keywords
Author Keywords:rare genetic disorder; high prevalence; novel mutation; founder effect; Alkaptonuria
KeyWords Plus:AORTIC-VALVE STENOSIS; IN-VITRO MODEL; HOMOGENTISIC ACID; OCHRONOTIC
ARTHROPATHY; ASCORBIC-ACID;ALCAPTONURIA; CHONDROCYTES; ARTHRITIS; PIGMENT; MAPS
Author Information
Reprint Address: Saravanan, MP (reprint author)
Stanley Med Coll, Dept Biochem, Madras 600001, Tamil Nadu, India.
Addresses:
[ 1 ] Bharathidasan Univ, Dept Biotechnol & Genet Engn, Tiruchchirappalli, Tamil Nadu, India
[ 2 ] Slovak Acad Sci, Inst Mol Physiol & Genet, Bratislava 83334, Slovakia
[ 3 ] Comenius Univ, Fac Nat Sci, Dept Mol Biol, Bratislava, Slovakia
[ 4 ] KAP Viswanatham Govt Med Coll, Dept Biochem, Tiruchchirappalli, Tamil Nadu, India
E-mail Addresses:mpsdoc2006@yahoo.co.in
Funding
Funding Agency
Grant Number
ERDF
ITMS 26240220071
VEGA AGENCY
2/0027/12
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Publisher
WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Categories / Classification
Research Areas:Genetics & Heredity
Web of Science Categories:Genetics & Heredity
Document Information
Document Type:Article
Language:English
Accession Number: WOS:000334030400001
PubMed ID: 24575791
ISSN: 0003-4800
eISSN: 1469-1809
Other Information
IDS Number: AE5LL
Cited References in Web of Science Core Collection: 43
Times Cited in Web of Science Core Collection: 1