Mutation Spectra Of The Itgb2 Gene In Iranian Families With Leukocyte Adhesion Deficiency Type 1

2174 words - 9 pages

Introduction

Leukocyte adhesion deficiency type 1 (OMIM # 116920) (LAD1) is a rare (1 in every 10,000 live births) autosomal recessive syndrome resulting from mutations in the gene encoding CD18 protein (the integrin beta 2 chain, ITGB2).
ITGB2 has 16 exons located on 21q22.3. This gene is involved in adhesion and transmigration of human leukocytes in vivo, and thus patients with LAD1 have absent or severely reduced expression of ITGB2 chain on the surface of their leukocytes resulting in impaired accumulation of myeloid leukocytes at extravascular sites. The product of this gene belongs to the integrin beta chain family of proteins. A given chain may combine with multiple partners, ...view middle of the document...

Early diagnosis of LAD1 is vital to the success of treatment and prevention of aggressive infections. The main aims of this study are uncovering variations using sequence analysis of the ITGB2 gene in Iranian patients with LADl. The results of this study can be used in prenatal diagnosis in subsequent pregnancies and genetic counseling for LAD1 patient.

Materials and Methods

Subjects

This study included 19 patients (10 boys and nine girls, ages between 60 days to 12 years) with initial diagnoses of LAD1 from consanguineous families. They were referred to the Children's Medical Center and Masih Daneshvari hospital having high levels of white blood cells in complete blood counts (CBC) (Table 1).
We obtained Blood samples from19 affected LAD1 and their parents after informed and written consent. Genomic DNA was prepared from whole blood by salting out method. Thirteen primer pairs were used to amplify 16 exons and exon–intron binderies of an ITGB2 gene under conditions available upon request. Amplifications of 50 µl Reactions were performed on a thermal cycler. PCR products were evaluated on 2% agarose gel, and purified PCR products were sequenced using the ABI 3130 DNA Analyzer (Applied Biosystems, Foster City, CA). Sequence analysis was performed using Chromas 2.4 and Lasergene (SeqMan ProV.1.7.0).

Results

Clinical and Laboratory Findings

The most common clinical signs were infection, inflammation of the umbilicus and delayed umbilical cord separation (usually after three weeks) in these LAD1 patients. CBC in these patients indicated neutrophil dysfunction and an increased number of blood cells. In most cases, omphalitis and Skin ulcers symptoms were seen in the early stages of the disease (Table 1).

Mutation detection

Mutation analysis carried out on ITGB2 gene sequences of 19 patients. After identification of mutation in an exon, sequencing was not performed to the remaining exons. DNA sequence analysis of ITGB2 gene in Iranian families, demonstrating an autosomal recessive form of LAD1, identified different types of mutations, including, four insertion/deletion and ten missense/nonsense mutations. Among the 19 families analyzed, ten different types of mutations previously reported were identified, including c.329-6C>A, c.382G>T, c.715G>A, c.843delC, c.897+1G>A, c.1062A>T, c.1143delC, c.1877+2T>C, c.1907delA and c.2147G>C. Sequence analysis of the ITGB2 gene revealed four novel mutations including; c.576dupC (Asn193GlnfsX72), c.706G>A (Gly236Arg), c.897+1G>T and c.1030G>T (Glu344*) (Table 2. Figure 1.). All variations were confirmed in parents as criers.

Figure 1. Sequence analysis of four novel variations in the gene ITGB2; Arrows indicates the location of mutations. A1, B1, C1 and D1 represent normal nucleotide sequences in the affected individuals. A2 (c.576dupC) and B2 (c.706G>A) indicate heterozygous variation in P6. C2 (c.897+1G>A, in P7 and P15) and C3 (c.897+1G>T, in P10) show splicing variant identified in intron 7. D2...

Other Essays Like Mutation spectra of the ITGB2 gene in Iranian families with Leukocyte Adhesion Deficiency type 1

The Importance Of Sharing Religious Rituals In The Home For Jewish Families

1617 words - 7 pages The Importance of Sharing Religious Rituals in the Home for Jewish Families The home is central to Judaism as it is the setting in which a husband and wife mature together and where children are taught about their religion through example and direct instruction. Both Orthodox and Liberal Jews will share rituals as a family at home but will not share the same attitudes and degree of discipline. This can lead to different

Right vs. Wrong: Type of Lies in the Adventures of Huckleberry Finn

1077 words - 5 pages history it is not uncommon for slave catchers to go out looking for runaway slaves and Huck and Jim run into this during their journey to Cairo. Huck decides to hide Jim under the blanket and say to the slave catchers that “it’s pap” under the blanket and he has “got the smallpox”, which was a deadly disease at that time period (pg101). The slave catchers tell Huck to go to the next town in fear of getting the virus and leave him with a twenty

1 . Building Long-Term Relationships with Customers a Company's Success in Establishing Long-Term Customer Relationships Typically Requires Close Working Relationships with Many Different Companies....

1089 words - 5 pages 1 . 1 . Building long-term relationships with customers A company's success in establishing long-term customer relationships typically requires close working relationships with many different companies. The act of developing long-term profitable customer relationship will not only create wealth for the company but is also another good way of ensuring the retention of customers and thereby the survival and profitability of the company. Michael

This Essay is on downs syndrom. It has causes of the disease, different treatments and how families cope with the disease

534 words - 3 pages Down syndrome is the most commonly occurring genetic condition in the world. One in every 800 births is a child with Down syndrome, which is approximately 5,000 births per year in the United States alone. Today, Down syndrome affects more than 350,000 people in the United States, and grows every day.Down syndrome is usually caused by an error in cell division called non-disjunction. Normally, at the time of conception a baby inherits genetic

Identify The Type Of Team Player You Are In Your Group. How Do You Facilitate Group Work?

464 words - 2 pages I am a team player that is very easy to work with. I come to find that I am now the team representative for both classes in AIU online. I don't like to use leader, so I am using representative. In reality, I am representing the group in one person. I have never been one, so this is a new experience for me. I am an honest person and will not take credit that should go to another member of the team.I am here to support my members and be here for

The Effects Of Divorce On Children And Families

1682 words - 7 pages partner” in the household (qtd. in Jurkovic et al. 1). This may include working at an early age, coming home to an empty house after school, and most of all dealing with the emotional stress of at least one broken hearted parent. As a child of a divorced family, an extreme amount of pressure is pushed into the situation. More often than not, at early ages children are asked who they would rather live with, Mom or Dad. In a sense, two adults are

Uv Rays and the Type of Uv Rays

605 words - 3 pages People that state tanning beds are harmful are often wrong. These people often aren’t educated about UV rays and the type of UV rays in tanning beds. Saying, for instance, the UV rays cause suppression of the immune system, cataracts, skin cancer, and/or premature aging of the skin. Comparing tanning beds to the sun. But tanning beds are a lot different from the sun. UV light is typically found as part of the radiation received by the

Approach to the Problem Type of Research Design

980 words - 4 pages ?” The Marketing Problem: “To determine the effective way of delivering the value proposition of IT Program.” Approach to the Problem 3 Main Components: 1. Value proposition content (3 Research Questions) 2. Competition (2 Research Questions) 3. Needs of potential customers (3 Research Questions) Type of Research Design Exploratory: ● Interviews with the schools principals Descriptive: ● Survey with potential customers

Compare The Way The Temple, David, Solomon And The Kings Of Judah Are Presented In The Books Of 1 And 2 Chronicles With The Parallel Discussion In The Books Of Samuel And Kings

1300 words - 6 pages Q: Compare the way the Temple, David, Solomon and the Kings of Judah are presented in the books of 1 and 2 Chronicles with the parallel discussion in the books of Samuel and Kings. Offer an explanation for any differences you may find.The Chronicler, author of Chronicles, bases much of his material on the books of Samuel-Kings. La Sor states 'Indeed, about one-half of the material in Chronicles is repeated virtually word for word from earlier

Explain How Eukaryotic Chromosomes Store a Unique Genotype, Discussing How the Processes of Independent Assortment, Mutation and Crossing over Contribute to Genetic Variation Amongst Individuals

2229 words - 9 pages disrupt genes if one chromosome has a working gene and the other doesn’t. When they cross over, both might end up with half a working gene which will result in both of them not being able to produce the amino acids that make a protein, that would have been encoded by such a gene. The offspring inheriting these mixed genes will then pass these on to their children. Mutation Inherited variation is the raw material from which organisms confronted

"Motifs of Amy Tan's 'The Joy Luck Club'" is about the motifs and themes in section 1 of Amy Tan's "The Joy Luck Club." It deals with motifs such as the color red, the five elements, and promises

468 words - 2 pages In the first section of The Joy Luck Club by Amy Tan, there are many motifs threaded throughout each of the four stories. One of which is the color red. The color red is very symbolic towards early Chinese culture and tradition.In the chapter, The Red Candle, the author explains everything in detail. She explains about the red columns in front of the house for decoration, the red dragons, the red wedding dress with the red wedding veil, the red

Related Papers

About Grains Peeling Machine Of The Type Described In Detail

526 words - 3 pages About Grains Peeling Machine of The Type Described in Detail Our company had researched and developed six model Grain Peeling Machine Types, following is introduction in detail. MTPZ-8×3 multifunctional compound peeling machine is one of the Grain Peeling Machine Types and main used in various grains peeling, degerming and polishing. It can process grains into peeled kernels once. MTPZ-8×3 multifunctional compound peeling machine can be used

Mutations In The Alpha 1,2 Mannosidase Gene

1073 words - 5 pages article Mutations in the Alpha 1,2-Mannosidase Gene, MAN1B1, Cause Autosomal-Recessive Intellectual Disability, Rafiq et al. present their findings of the gene that they investigated causes autosomal recessive intellectual disability [ARID]. [5] In this study, the genetic setup of five families with high proportion of consanguinity (See Table 1) with individuals having ARID was analyzed. To find out which gene was the cause of the ID, a specific

Families In The 1960’s And Today

639 words - 3 pages stronger as a family. Families in the 1960’s and Today There is quite a big difference in families from the 1960’s, and the families of today. Many of the changes from back in 1960 have to do with the parents and keeping family together. These differences have changed since then and will continue to change as time changes. The families today are mostly single parent homes with just the mother’s and the children. On the other hand when the

Type Of Iron Ore Crusher In India

622 words - 3 pages , Portable Manufacturer and Exporter of Magnetic Separator, Overband Magnetic Separator, Drum Type Magnetic Separator, Portable Magnetic Separator, Electro Suspension ZENTIH crusher for sale used in mining industry with plant ZENTIH with full name: ZENITH coming from China is a professional manufacturer of stone crusher, grinding mill, optional equipments, and related mining equipments for Stone Crusher Spare Parts - Grease Type Of Stone Crusher We