title: GALNS mutations in Indian patients with mucopolysaccharidosis IVA.
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.
authors.affiliation: Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.
authors.forename: Abdul Mueed
authors.initials: AM
authors.lastname: Bidchol
authors.forename: Ashwin
authors.initials: A
authors.lastname: Dalal
authors.forename: Hitesh
authors.initials: H
authors.lastname: Shah
authors.forename: Suryanarayana
authors.initials: S
authors.lastname: S
authors.forename: Sheela
authors.initials: S
authors.lastname: Nampoothiri
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kabra
authors.forename: Neerja
authors.initials: N
authors.lastname: Gupta
authors.forename: Sumita
authors.initials: S
authors.lastname: Danda
authors.forename: Kalpana
authors.initials: K
authors.lastname: Gowrishankar
authors.forename: Shubha R
authors.initials: SR
authors.lastname: Phadke
authors.forename: Seema
authors.initials: S
authors.lastname: Kapoor
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kamate
authors.forename: I C
authors.initials: IC
authors.lastname: Verma
authors.forename: Ratna Dua
authors.initials: RD
authors.lastname: Puri
authors.forename: V H
authors.initials: VH
authors.lastname: Sankar
authors.forename: A Radha Rama
authors.initials: AR
authors.lastname: Devi
authors.forename: S J
authors.initials: SJ
authors.lastname: Patil
authors.forename: Prajnya
authors.initials: P
authors.lastname: Ranganath
authors.forename: S Jamal Md Nurul
authors.initials: SJ
authors.lastname: Jain
authors.forename: Meenal
authors.initials: M
authors.lastname: Agarwal
authors.forename: Ankur
authors.initials: A
authors.lastname: Singh
authors.forename: Pallavi
authors.initials: P
authors.lastname: Mishra
authors.forename: Parag M
authors.initials: PM
authors.lastname: Tamhankar
authors.forename: Puthiya Mundyat
authors.initials: PM
authors.lastname: Gopinath
authors.forename: H A
authors.initials: HA
authors.lastname: Nagarajaram
authors.forename: Kapaettu
authors.initials: K
authors.lastname: Satyamoorthy
authors.forename: Katta Mohan
authors.initials: KM
authors.lastname: Girisha
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D002811:Chondroitinsulfatases / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D005260:Female; D005787:Gene Frequency; D023061:Gene Order; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D002811:Chondroitinsulfatases; C102295:GALNS protein, human
keywords: GALNS gene; India; diagnosis; genetics; morquio syndrome A; mucopolysaccharidosis IVA; mutation