Identification of DKC1 gene mutation in an Indian patient

Tamhankar, Parag M; Zhao, Meina; Kanegane, Hirokazu; Phadke, Shubha R.

doi:10.1007/s12098-009-0300-1

Cited by 3 publications

(2 citation statements)

References 7 publications

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“…The mutation c.1058C[T (p.A353V) in DKC1 gene is the commonest mutation in patients with dyskeratosis congenita and occurs due to this mechanism. This has been demonstrated in a child in our study (Tamhankar et al 2010). Similarly the denovo heterozygous mutations p.R282H and p.R282C in TINF2 gene also occur in a CpG hotspot region.…”

Section: Molecular Diversity In Genetic Hematological Syndromes In Indiasupporting

confidence: 85%

Abstracts of the Lectures During Haematocon 2013

2013

Indian J Hematol Blood Transfus

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Genetic studies have been included as one of the prerequisites for classification of acute leukemias in the WHO classification of tumors of hematopoietic and lymphoid tissues along with morphology and immunophenotypic features. The cytogenetic and molecular genetic studies are required at the time of diagnosis, not only for recognition of specific genetically defined entities but also for risk stratification and define a baseline against which future studies can be judged to assess clinical progression and response to treatment. Recurring chromosomal translocations that were included in the WHO classification of acute leukemias in 2001 provided clues to better understanding of the process of leukemogenesis and the recognition of various genes located at the breakpoints of these translocations. Many of these chromosomal changes are consistently associated with either myeloid or lymphoid leukemias, and correlate with specific morphologic or immunophenotypic subtypes.Acute lymphoblastic leukemia (ALL) is a heterogenous disease with distinct biological and prognostic groupings. The leukemia is characterized by proliferation of immature B or T cells as a result of various genetic lesions in blood progenitor cells. These genetic lesions are known to have prognostic ramifications. Approximately 75 % of childhood ALL harbor genetic aberrations that are detectable by karyotyping, FISH, or molecular techniques. These include the t(12;21)(p13;q22) and hyperdiploidy which are associated with a good prognosis on one hand and MLL gene rearrangements, e.g. t(4;11) (q21;q23), low hypodiploidy (\40 chromosomes), t(17;19) (q22;p13) (TCF3-HLF),intrachromosomal amplification of chromosome 21 (iAMP21) and t(9;22) (q34;q11) (BCR-ABL) that are associated with poor prognosis. The development of microarray technologies to profile gene expression and structural genetic alterations in a genome-wide and high-resolution fashion have revolutionized our ability to identify genetic abnormalities and have lead to recognition of new entities like BCR/ABL1 like ALL. The development of next-generation sequencing (NGS) technologies have lead to identification of mutations in an array of genes like the PAX5, IKZF1, JAK1/2, CRLF2, IL7R,CREBBP, TP53 and kinase rearrangements and mutations which can be potential molecular targets for the treatment of ALL. Also NGS technology is being used in monitoring the minimal residual disease in ALL.The molecular classification of acute myeloid leukemia (AML) includes recurrent chromosomal structural variations which are well established as both diagnostic and prognostic markers. Patients having PML-RARA, RUNX1-RUNX1T1 and MYH11CBFB fusions are associated with good prognosis and those with 3q abnormalities, monosomy 7, deletion 5q, t(6;9)(p22;q34) are associated with a poor prognosis. However nearly 50 % of AML samples have a normal karyotype and most of these patients lacked structural abnormalities even when assessed with high density comparative genomic hybridization or single nucleotide polymorphism (SNP) arra...

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Section: Molecular Diversity In Genetic Hematological Syndromes In Indiasupporting

confidence: 85%

Abstracts of the Lectures During Haematocon 2013

2013

Indian J Hematol Blood Transfus

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“…We also found 13 variants of DKC1 in Asia with 100% male ( 7 , 9 , 13 , 20 , 23 , 28 , 32 , 35 , 36 , 40 ), 52 variants in non-Asia with 84.8% male ( 1 , 8 , 10 – 14 , 16 – 19 , 21 , 24 – 26 , 29 , 31 , 33 , 34 , 37 , 38 , 41 , 42 , 44 , 45 ), and 10 variants with unknown nationality ( 3 , 4 , 30 ). Asians develop DC at a younger age than non-Asians, between 4.3 and 46 years old ( 1 , 7 – 12 , 14 , 16 – 24 , 26 , 28 , 29 , 31 – 35 , 38 – 42 ).…”

Section: Discussionsupporting

confidence: 54%

Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad

Wang

Xiong

et al. 2022

Front. Pediatr.

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BackgroundDyskeratosis congenita (DC) is a rare inheritable disorder characterized by bone marrow failure and mucocutaneous triad (reticular skin pigmentation, nail dystrophy, and oral leukoplakia). Dyskeratosis congenita 1 (DKC1) is responsible for 4.6% of the DC with an X-linked inheritance pattern. Almost 70 DKC1 variations causing DC have been reported in the Human Gene Mutation Database.ResultsHere we described a 14-year-old boy in a Chinese family with a phenotype of abnormal skin pigmentation on the neck, oral leukoplakia, and nail dysplasia in his hands and feet. Genetic analysis and sequencing revealed hemizygosity for a recurrent missense mutation c.1156G > A (p.Ala386Thr) in DKC1 gene. The heterozygous mutation (c.1156G > A) from his mother and wild-type sequence from his father were obtained in the same site of DKC1. This mutation was determined as disease causing based on silico software, but the pathological phenotypes of the proband were milder than previously reported at this position (HGMDCM060959). Homology modeling revealed that the altered amino acid was located near the PUA domain, which might affect the affinity for RNA binding.ConclusionThis DKC1 mutation (c.1156G > A, p.Ala386Thr) was first reported in a Chinese family with mucocutaneous triad phenotype. Our study reveals the pathogenesis of DKC1 c.1156G > A mutation to DC with a benign phenotype, which expands the disease variation database, the understanding of genotype–phenotype correlations, and facilitates the clinical diagnosis of DC in China.

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