Large Region of Homozygous (ROH) Identified in Indian Patients with Autosomal Recessive Limb-Girdle Muscular Dystrophy with p.Thr182Pro Variant in SGCB Gene

被引:0
|
作者
Manjunath, V. [1 ,2 ]
Thenral, S. G. [1 ]
Lakshmi, B. R. [3 ]
Nalini, Atchayaram [4 ]
Bassi, A. [1 ]
Karthikeyan, K. Priya [3 ]
Piyusha, K. [1 ]
Menon, R. [1 ]
Malhotra, A. [1 ]
Praveena, L. S. [1 ]
Anjanappa, R. M. [1 ]
Murugan, S. M. Sakthivel [1 ]
Polavarapu, Kiran [4 ]
Bardhan, Mainak [4 ]
Preethish-Kumar, V. [4 ]
Vengalil, Seena [4 ]
Nashi, Saraswati [4 ]
Sanga, S. [5 ]
Acharya, M. [5 ]
Raju, R. [2 ]
Pai, V. R. [2 ]
Ramprasad, V. L. [1 ]
Gupta, R. [1 ]
机构
[1] MedGenome Labs Pvt Ltd, Bangalore, India
[2] Yenepoya, Yenepoya Med Coll, Mangalore, India
[3] Mol Diagnost Counseling Care & Res Ctr MDCRC, Coimbatore, Tamil Nadu, India
[4] Natl Inst Mental Hlth & Neurosci, Bangalore, India
[5] Natl Inst Biomed Genom, Kolkata, India
关键词
GLYCOPROTEIN COMPLEX; ASSOCIATION;
D O I
10.1155/2023/4362273
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The sarcoglycanopathies are autosomal recessive limb-girdle muscular dystrophies (LGMDs) caused by the mutations in genes encoding the alpha, beta, gamma, and delta proteins which stabilizes the sarcolemma of muscle cells. The clinical phenotype is characterized by progressive proximal muscle weakness with childhood onset. Muscle biopsy findings are diagnostic in confirming dystrophic changes and deficiency of one or more sarcoglycan proteins. In this study, we summarized 1,046 LGMD patients for which a precise diagnosis was identified using targeted sequencing. The most frequent phenotypes identified in the patients are LGMDR1 (19.7%), LGMDR4 (19.0%), LGMDR2 (17.5%), and MMD1 (14.5%). Among the reported genes, each of CAPN3, SGCB, and DYSF variants was reported in more than 10% of our study cohort. The most common variant SGCB p.Thr182Pro was identified in 146 (12.5%) of the LGMD patients, and in 97.9% of these patients, the variant was found to be homozygous. To understand the genetic structure of the patients carrying SGCB p.Thr182Pro, we genotyped 68 LGMD patients using a whole genome microarray. Analysis of the array data identified a large similar to 1 Mb region of homozygosity (ROH) (chr4:51817441-528499552) suggestive of a shared genomic region overlapping the recurrent missense variant and shared across all 68 patients. Haplotype analysis identified 133 marker haplotypes that were present in similar to 85.3% of the probands as a double allele and absent in all random controls. We also identified 5 markers (rs1910739, rs6852236, rs13122418, rs13353646, and rs6554360) which were present in a significantly higher proportion in the patients compared to random control set (n = 128) and the population database. Of note, admixture analysis was suggestive of greater proportion of West Eurasian/European ancestry as compared to random controls. Haplotype analysis and frequency in the population database indicate a probable event of founder effect. Further systematic study is needed to identify the communities and regions where the SGCB p.Thr182Pro variant is observed in higher proportions. After identifying these communities and//or region, a screening program is needed to identify carriers and provide them counselling.
引用
收藏
页数:10
相关论文
共 37 条
  • [21] Three novel recessive DYSF mutations identified in three patients with muscular dystrophy, limb-girdle, type 2B
    Okubo, Mariko
    Iide, Aritoshi
    Hayashi, Shinichiro
    Mori-Yoshimura, Madoka
    Oya, Yasushi
    Watanabe, Akihiro
    Arahata, Hajime
    El Sherif, Rasha
    Noguchi, Satoru
    Nishino, Ichizo
    JOURNAL OF THE NEUROLOGICAL SCIENCES, 2018, 395 : 169 - 171
  • [22] Two Novel Variants of the CAPN3 Gene in Chinese Patients with Limb-Girdle Muscular Dystrophy Recessive 1
    Zhang, Lulu
    Zhang, Yi
    Han, Chunru
    Jiang, Juean
    Jiang, Jianhua
    Cai, Xiuying
    Yu, Liqiang
    Qi, Huan
    Fang, Qi
    Ding, Dongxue
    HUMAN HEREDITY, 2024, 89 (01) : 52 - 59
  • [23] A new locus for autosomal recessive limb-girdle muscular dystrophy in a large consanguineous Tunisian family maps to chromosome 19q13.3
    Driss, A
    Amouri, R
    Ben Hamida, C
    Souilem, S
    Gouider-Khouja, N
    Ben Hamida, M
    Hentati, F
    NEUROMUSCULAR DISORDERS, 2000, 10 (4-5) : 240 - 246
  • [24] CONFIRMATION OF THE 2P LOCUS FOR THE MILD AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR-DYSTROPHY GENE (LGMD2B) IN 3 FAMILIES ALLOWS REFINEMENT OF THE CANDIDATE REGION
    PASSOSBUENO, MR
    BASHIR, R
    MOREIRA, ES
    VAINZOF, M
    MARIE, SK
    VASQUEZ, L
    IUGHETTI, P
    BAKKER, E
    KEERS, S
    STEPHENSON, A
    STRACHAN, T
    MAHNEH, I
    WEISSENBACH, J
    BUSHBY, K
    ZATZ, M
    GENOMICS, 1995, 27 (01) : 192 - 195
  • [25] Homozygous TRAPPC11 truncating variant revealing segmental uniparental disomy of chromosome 4 as a cause of a recessive limb-girdle muscular dystrophy-18
    Hadouiri, Nawale
    Thomas, Quentin
    Darmency, Veronique
    Dulieu, Veronique
    De Rougemont, Marie-Gabrielle Mourot
    Bruel, Ange-Line
    Duffourd, Yannis
    Lecoquierre, Francois
    Colomb, Benoit
    Perez-Martin, Stephanie
    Ornetti, Paul
    Blanchard, Olivier
    Sorlin, Arthur
    Philippe, Christophe
    Faivre, Laurence
    Vitobello, Antonio
    Thauvin-Robinet, Christel
    CLINICAL GENETICS, 2021, 100 (05) : 643 - 644
  • [26] A COMMON MISSENSE MUTATION IN THE ADHALIN GENE IN 3 UNRELATED BRAZILIAN FAMILIES WITH A RELATIVELY MILD FORM OF AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR-DYSTROPHY
    BUENO, MRP
    MOREIRA, ES
    VAINZOF, M
    CHAMBERLAIN, J
    MARIE, SK
    PEREIRA, L
    AKIYAMA, J
    ROBERDS, SL
    CAMPBELL, KP
    ZATZ, M
    HUMAN MOLECULAR GENETICS, 1995, 4 (07) : 1163 - 1167
  • [27] A novel homozygous variant (c.5876T > C: p. Leu1959Pro) in DYSF segregates with limb-girdle muscular dystrophy: a case report
    Hamed Hesami
    Serwa Ghasemi
    Golnaz Houshmand
    Yalda Nilipour
    Mahshid Hesami
    Alireza Biglari
    Shahriar Nafissi
    Majid Maleki
    Samira Kalayinia
    BMC Musculoskeletal Disorders, 25
  • [28] A novel homozygous variant (c.5876T > C: p. Leu1959Pro) in DYSF segregates with limb-girdle muscular dystrophy: a case report
    Hesami, Hamed
    Ghasemi, Serwa
    Houshmand, Golnaz
    Nilipour, Yalda
    Hesami, Mahshid
    Biglari, Alireza
    Nafissi, Shahriar
    Maleki, Majid
    Kalayinia, Samira
    BMC MUSCULOSKELETAL DISORDERS, 2024, 25 (01)
  • [29] The gene for autosomal dominant Limb-Girdle Muscular Dystrophy and Paget Disease of Bone in a large family maps to a unique locus on 9p22.3-q12.
    Kovach, MJ
    Kimonis, VE
    Leal, S
    Waggoner, B
    Salam, A
    Khadori, R
    Gelber, D
    AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (04) : 323 - 323
  • [30] Identification of lamin A/C (LMNA) gene mutations in Korean patients with autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy 1B
    C.-S. Ki
    J.S. Hong
    G.-Y. Jeong
    K. J. Ahn
    K.-M. Choi
    D.-K. Kim
    J.-W. Kim
    Journal of Human Genetics, 2002, 47 : 225 - 228