GALNS mutations in Indian patients with mucopolysaccharidosis IVA

Abdul Mueed Bidchol, Ashwin Dalal, Hitesh Shah, Suryanarayana S, Sheela Nampoothiri, Madhulika Kabra, Neerja Gupta, Sumita Danda, Kalpana Gowrishankar, Shubha R. Phadke, Seema Kapoor, Mahesh Kamate, I. C. Verma, Ratna Dua Puri, V. H. Sankar, A. Radha Rama Devi, S. J. Patil, Prajnya Ranganath, S. Jamal Md Nurul Jain, Meenal Agarwal & 7 others Ankur Singh, Pallavi Mishra, Parag M. Tamhankar, Puthiya Mundyat Gopinath, H. A. Nagarajaram, Kapaettu Satyamoorthy, Katta Mohan Girisha

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Mucopolysaccharidosis IV A (Morquio syndrome A, 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. We report twenty-two novel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191Asp, 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.120+1G>C, c.1003-3C>G, c.1139+1G>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.

Original languageEnglish
Pages (from-to)2793-2801
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume164
Issue number11
DOIs
Publication statusPublished - 01-11-2014

Fingerprint

Mucopolysaccharidoses
Mucopolysaccharidosis IV
Mutation
Exons
N-acetylglucosamine-6-sulfatase
Alleles
Lysosomal Storage Diseases
Acetylgalactosamine
Frameshift Mutation
Nonsense Codon
Population
Genes
India
Costs and Cost Analysis

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Bidchol, Abdul Mueed ; Dalal, Ashwin ; Shah, Hitesh ; S, Suryanarayana ; Nampoothiri, Sheela ; Kabra, Madhulika ; Gupta, Neerja ; Danda, Sumita ; Gowrishankar, Kalpana ; Phadke, Shubha R. ; Kapoor, Seema ; Kamate, Mahesh ; Verma, I. C. ; Puri, Ratna Dua ; Sankar, V. H. ; Devi, A. Radha Rama ; Patil, S. J. ; Ranganath, Prajnya ; Jain, S. Jamal Md Nurul ; Agarwal, Meenal ; Singh, Ankur ; Mishra, Pallavi ; Tamhankar, Parag M. ; Gopinath, Puthiya Mundyat ; Nagarajaram, H. A. ; Satyamoorthy, Kapaettu ; Girisha, Katta Mohan. / GALNS mutations in Indian patients with mucopolysaccharidosis IVA. In: American Journal of Medical Genetics, Part A. 2014 ; Vol. 164, No. 11. pp. 2793-2801.
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abstract = "Mucopolysaccharidosis IV A (Morquio syndrome A, 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. We report twenty-two novel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191Asp, 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.120+1G>C, c.1003-3C>G, c.1139+1G>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.",
author = "Bidchol, {Abdul Mueed} and Ashwin Dalal and Hitesh Shah and Suryanarayana S and Sheela Nampoothiri and Madhulika Kabra and Neerja Gupta and Sumita Danda and Kalpana Gowrishankar and Phadke, {Shubha R.} and Seema Kapoor and Mahesh Kamate and Verma, {I. C.} and Puri, {Ratna Dua} and Sankar, {V. H.} and Devi, {A. Radha Rama} and Patil, {S. J.} and Prajnya Ranganath and Jain, {S. Jamal Md Nurul} and Meenal Agarwal and Ankur Singh and Pallavi Mishra and Tamhankar, {Parag M.} and Gopinath, {Puthiya Mundyat} and Nagarajaram, {H. A.} and Kapaettu Satyamoorthy and Girisha, {Katta Mohan}",
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Bidchol, AM, Dalal, A, Shah, H, S, S, Nampoothiri, S, Kabra, M, Gupta, N, Danda, S, Gowrishankar, K, Phadke, SR, Kapoor, S, Kamate, M, Verma, IC, Puri, RD, Sankar, VH, Devi, ARR, Patil, SJ, Ranganath, P, Jain, SJMN, Agarwal, M, Singh, A, Mishra, P, Tamhankar, PM, Gopinath, PM, Nagarajaram, HA, Satyamoorthy, K & Girisha, KM 2014, 'GALNS mutations in Indian patients with mucopolysaccharidosis IVA', American Journal of Medical Genetics, Part A, vol. 164, no. 11, pp. 2793-2801. https://doi.org/10.1002/ajmg.a.36735

GALNS mutations in Indian patients with mucopolysaccharidosis IVA. / Bidchol, Abdul Mueed; Dalal, Ashwin; Shah, Hitesh; S, Suryanarayana; Nampoothiri, Sheela; Kabra, Madhulika; Gupta, Neerja; Danda, Sumita; Gowrishankar, Kalpana; Phadke, Shubha R.; Kapoor, Seema; Kamate, Mahesh; Verma, I. C.; Puri, Ratna Dua; Sankar, V. H.; Devi, A. Radha Rama; Patil, S. J.; Ranganath, Prajnya; Jain, S. Jamal Md Nurul; Agarwal, Meenal; Singh, Ankur; Mishra, Pallavi; Tamhankar, Parag M.; Gopinath, Puthiya Mundyat; Nagarajaram, H. A.; Satyamoorthy, Kapaettu; Girisha, Katta Mohan.

In: American Journal of Medical Genetics, Part A, Vol. 164, No. 11, 01.11.2014, p. 2793-2801.

Research output: Contribution to journalArticle

TY - JOUR

T1 - GALNS mutations in Indian patients with mucopolysaccharidosis IVA

AU - Bidchol, Abdul Mueed

AU - Dalal, Ashwin

AU - Shah, Hitesh

AU - S, Suryanarayana

AU - Nampoothiri, Sheela

AU - Kabra, Madhulika

AU - Gupta, Neerja

AU - Danda, Sumita

AU - Gowrishankar, Kalpana

AU - Phadke, Shubha R.

AU - Kapoor, Seema

AU - Kamate, Mahesh

AU - Verma, I. C.

AU - Puri, Ratna Dua

AU - Sankar, V. H.

AU - Devi, A. Radha Rama

AU - Patil, S. J.

AU - Ranganath, Prajnya

AU - Jain, S. Jamal Md Nurul

AU - Agarwal, Meenal

AU - Singh, Ankur

AU - Mishra, Pallavi

AU - Tamhankar, Parag M.

AU - Gopinath, Puthiya Mundyat

AU - Nagarajaram, H. A.

AU - Satyamoorthy, Kapaettu

AU - Girisha, Katta Mohan

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Mucopolysaccharidosis IV A (Morquio syndrome A, 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. We report twenty-two novel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191Asp, 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.120+1G>C, c.1003-3C>G, c.1139+1G>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.

AB - Mucopolysaccharidosis IV A (Morquio syndrome A, 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. We report twenty-two novel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191Asp, 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.120+1G>C, c.1003-3C>G, c.1139+1G>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.

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JF - American Journal of Medical Genetics, Part A

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