GALNS Mutations in Indian Patients With Mucopolysaccharidosis IVA

Bidchol, Abdul Mueed and Shah, Hitesh and Satyamoorthy, K and Girisha, KM (2014) GALNS Mutations in Indian Patients With Mucopolysaccharidosis IVA. American Journal of Medical Genetics Part - A, 9999. pp. 1-9.

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Abstract

Mucopolysaccharidosis IVA(Morquio syndromeA,MPS IVA) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine- 6-sulfatase (GALNS). The mutation spectrum in this condition is yet to be determined in Indians. We aimed to analyze the mutations in the GALNS gene in Asian Indians with MPS IVA. All the exons and the adjacent intronic regions of the gene were amplified and sequenced in sixty-eight unrelated Indian families. We identified 136 mutant alleles comprising of 40 different mutations.Wereport twenty-twonovel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191- Asp, p.Asn204Thr, p.Gly188Ser, p.Phe216Ser, p.Trp230Cys, p.Ala291Ser, p.Gly317Arg, p.His329Pro, p.Arg386Ser, p. Glu450Gly, p.Cys501Ser), three splice-site variants (c.120þ1G >C, c.1003-3C>G, c.1139þ1G>A), one nonsense mutation (p.Gln414 * ) and one frameshift mutation (p.Pro420Leufs * 440). Eighteen mutations have been reported earlier. Among these p. Ser287Leu (8.82%), p.Phe216Ser (7.35%), p.Asn32Thr (6.61%) and p.Ala291Ser (5.88%) were the most frequent mutations in Indian patients but were rare in the mutational profiles reported in other populations. These results indicate that the Indian patients may have a distinct mutation spectrum compared to those of other populations. Mutant alleles in exon 1, 7 and 8 accounted for 44.8% of the mutations, and sequencing of these exons initially may be a cost-effective approach in Asian Indian patients. This is the largest study on molecular analysis of patients with MPS IVA reported in the literature, and the first report from India.

Item Type: Article
Uncontrolled Keywords: Diagnosis; GALNS gene; genetics; India; morquio syndrome A; mucopolysaccharidosis IVA; mutation.
Subjects: Life Sciences > MLSC Manipal
Medicine > KMC Manipal > Orthopaedics
Medicine > KMC Manipal > Paediatrics
Depositing User: KMC Manipal
Date Deposited: 25 Sep 2014 10:15
Last Modified: 25 Sep 2014 10:15
URI: http://eprints.manipal.edu/id/eprint/140732

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