Mutation Analysis of Five Japanese Families with Wiskott-Aldrich Syndrome and Determination of the Family Members' Carrier Status Using Three Different Methods

ObjectivesTrichotillomania (TTM) is a psychiatric syndrome characterised by the inability to control repetitive hair pulling. Psychiatric data reveal that TTM is not usually prevalent among all family members of patients, and so far only one case of familial TTM has been reported.MethodsIn this study, we report a case of familial TTM that afflicted four sisters and discuss the importance of genetic factors in this disorder.ResultsThis report suggests that, similar to many other psychiatric disorders, TTM can be detected in other family members and that genetic factors not only have a significant role in the development of such disorders but also in determination of the disorder subtype. This report also shows that the comorbidities in one member of the family might predict the existence of comorbidities in other members. On the basis of response to medication.Conclusionthe authors suggest that a genetic disorder like polymorphism in serotonin receptors or dopamine can cause such a disorder.

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Use of CSGE, TspRI- RFLP and Western Blot in Carrier Detection in an Indian Family with Type I Glanzmann Thrombasthenia.

Blood ◽

10.1182/blood.v108.11.3975.3975 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3975-3975 ◽

Cited By ~ 1

Author(s):

Meganathan Kannan ◽

Firdos Ahmad ◽

Rajive Kumar ◽

Ved P. Choudhry ◽

Renu Saxena

Keyword(s):

Flow Cytometry ◽

Western Blot ◽

Family Members ◽

Carrier Detection ◽

Carrier Status ◽

Type I ◽

Restriction Digestion ◽

Glanzmann Thrombasthenia ◽

The Family ◽

Abnormal Band

Abstract Glanzmann Thrombasthenia (GT) is an inherited, autosomal recessive, bleeding disorder which is characterized by absent/reduced platelet Glycoprotein IIb/IIIa. The sub classification of GT into Types I, II and III is based on the levels of GPIIb/IIIa by flow cytometry. Type I is the most severe form of GT and is found to be most common in north Indian population. Since not much study is available on carrier detection based on western blot analysis, it is suggested to confirm the defect in carriers by molecular diagnosis. Here we present a carrier status using TspRI in a family with Glanzmann Thrombasthenia patient. Glanzmann Thrombasthenia was diagnosed in a patient with bleeding manifestations accompanied by absent platelet aggregation, secondary to ADP, ADR, Arachidonic acid and collagen. The patient was sub typed as Type I based on flow cytometry analysis as he had absent GPIIb/IIIa. Patient’s DNA was analyzed for mutation in both the gpIIb and gpIIIa genes by CSGE, followed by sequencing. The patient was found to have mutation, CTG>CCG at exon 12 of GPIIb gene. The mutation caused amino acid change from Leu to Pro in the GPIIb protein. The same mutation was looked for in all the family members (Both parents and two siblings) using CSGE and by TspRI- RFLP analysis. Both the parents and siblings were heterozygous for this mutation, where as patient was homozygous (Fig 1). As this mutation is not present in the normal individuals and is not reported earlier, this considers being a novel mutation. Presence of abnormal protein in the family members was revealed by western blot analysis for GPIIb (Fig 2). The same mutation is being looked for in more number of patients with Glanzmann Thrombasthenia using TspRI- RFLP. So far, a total of two out of 25 GT patients found to carry this mutation. It is possible that abnormal GPIIb protein by western blot in family members may reflect their carrier status. It is also postulated that western blot and CSGE of GPIIb and IIIa in parents/siblings may detect carrier status in Glanzmann Thrombasthenia. Fig 1: Carrier detection by restriction digestion using TspRI Fig 1:. Carrier detection by restriction digestion using TspRI Fig 2: Immunoblot followed by chemiluminescent detection shows absent/reduced protein in patient and abnormal band pattern in the family members Fig 2:. Immunoblot followed by chemiluminescent detection shows absent/reduced protein in patient and abnormal band pattern in the family members

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Fluorescent PCR Based Gene Dose Assessment for Detection of Deletion Mutations in the FIX Gene Among Carriers of Hemophilia B.

Blood ◽

10.1182/blood.v114.22.3486.3486 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3486-3486

Author(s):

Eunice Sindhuvi Edison ◽

G. Sankari Devi ◽

G. Jayandharan ◽

Shaji R Velayudhan ◽

Auro Viswabandya ◽

...

Keyword(s):

Linkage Analysis ◽

Real Time ◽

Real Time Pcr ◽

Gene Dosage ◽

Family Members ◽

Peak Height ◽

Hemophilia B ◽

Carrier Status ◽

Fluorescent Pcr ◽

The Family

Abstract Abstract 3486 Poster Board III-423 Haemophilia B (HB), an X linked inherited disorder is caused by heterogeneous mutations in the F9 gene. Approximately 3% of hemophilia B patients have major deletions in the F9 gene. Gross and small deletions in the F9 gene in HB affected males are easily detected by PCR but detecting the carrier state of females in the family is challenging due to the presence of the normal allele. Different methods like linkage analysis, real time PCR and MLPA have been used to assess the carrier status in this situation. Linkage analysis is limited by the availability of informative markers and adequate number of family members. Real time PCR involves standardisation and preparation of calibration curves for each run. Although MLPA is a better alternative, it can be time consuming and involves multiple steps. We have therefore developed a fluorescent PCR based gene dosage approach which is simple, rapid and cost-effective for determining the carrier status of females in families with deletions in the F9 gene. 200ng of DNA extracted by standard protocols was used for amplification with primers designed to amplify a 160bp product from exon h in the F9 gene. One of the primers was fluorescently labelled. Amplification was carried out using these primers for 20 cycles only and the amplified product was subjected to capillary electrophoresis on an ABI 310 genetic analyser. A 230 bp fragment in the albumin gene was used as the control. Analysis was done using Genescan and Genotyper software. The ratio between the peak heights of the exon h in the F9 and control genes in the patient samples were normalised to a normal control. Five families with deletional HB were analysed (in toto deletion-1; Ex g-h – 1; Ex g-poly A-1; Ex h-poly A-2). The ratios in the probands and the family members are presented in the table. Out of eight females analysed, 6 were carriers and 2 were normal. The mean ratio in the carriers was 0.49±0.08 and 0.75±0.05 in the normal. Deletions are not uncommon in HB and deletions involving the exon g and h constitute a major group. Among 212 families with HB assessed at our centre, we have identified large deletions in 8 families (3.7%). It is interesting to note that all except one of these deletional mutations involved exon h. This method confirmed the presence of these deletions in the males and helped us to identify the carrier status of the females in the family. Identification of carrier status of females with deletions in F9 gene by gene dosage Subject ID Peak height of Exh in F9 Peak height of albumin Normalised Ratio Interpretation HB5 284 442 0.59 Carrier HB6 305 489 0.57 Carrier HB22 188 372 0.47 Carrier HB63 85 165 0.48 Carrier HB129 247 295 0.78 Normal HB238 94 326 0.4 Carrier HB280 372 679 0.77 Normal HB384 202 670 0.4 Carrier Disclosures: No relevant conflicts of interest to declare.

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Determination of Carrier Status for the Wiskott-Aldrich Syndrome by Flow Cytometric Analysis of Wiskott-Aldrich Syndrome Protein Expression in Peripheral Blood Mononuclear Cells

The Journal of Immunology ◽

10.4049/jimmunol.165.2.1119 ◽

2000 ◽

Vol 165 (2) ◽

pp. 1119-1122 ◽

Cited By ~ 29

Author(s):

Masafumi Yamada ◽

Tadashi Ariga ◽

Nobuaki Kawamura ◽

Koji Yamaguchi ◽

Makoto Ohtsu ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Mononuclear Cells ◽

Flow Cytometric Analysis ◽

Carrier Status ◽

Peripheral Blood Mononuclear ◽

Wiskott Aldrich Syndrome ◽

Flow Cytometric ◽

Blood Mononuclear Cells ◽

Syndrome Protein

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Features of professional self-determination in various types of families (on the material of dynasties)

Вестник Костромского государственного университета им Н А Некрасова ◽

10.34216/2073-1426-2019-25-2-52-56 ◽

2019 ◽

pp. 52-56

Author(s):

Nikolay V. Shamanin ◽

Vitaliy Ye. Lapshin

Keyword(s):

Professional Development ◽

Family Members ◽

Self Determination ◽

Lag Effect ◽

The Family ◽

Professional Self ◽

The Individual ◽

Determining Factor

This article addresses the problem of determining the professional self-determination of younger family members. The article provides an analysis of the views of researchers on the role of the family in the professional development of an individual. The article deals with the problems of professional self-determination in dynastic and non-dynastic families. The question arises, whether the family is a support for its younger members on the basis of which, successful formation of professional qualities of the individual takes place, or the family may produce a "lag effect", ignoring inclinations, flairs and interests of the child. The study allows the authors to conclude that there is a transgenerative transference in the professional self-determination of the individual. The authors suggest that transgenerative transference is the main determining factor of professional self-determination in dynastic families, determining the choice of a profession by younger members of a dynastic family. It has been suggested that transformational phenomena occur in the process of professional self-determination of younger family members according to the types "inversion" (inversion), "hypertrophy" (amplification) and "deformation (distortion)".

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RESILIENSI DALAM KELUARGA: PERSPEKTIF PSIKOLOGI

Psikoislamedia Jurnal Psikologi ◽

10.22373/psikoislamedia.v2i1.1829 ◽

2017 ◽

Vol 2 (1) ◽

pp. 96

Author(s):

Marty Mawarpury ◽

Mirza Mirza

Keyword(s):

Social Context ◽

Family Members ◽

Family Resilience ◽

Ecological Perspective ◽

The Social ◽

The Family ◽

Generation Family ◽

System Review ◽

Main Activity

The family is the smallest institution in society. A generation is forming from a family. That is why, the building of a family must strong to produce a formidable generation. Family toughness is determined by the foundation of the family builder. Resilience is often defined as endurance. Resilience is generally defined as the ability to overcome adversity, or to thrive despite challenges and difficulties in life. The concept of resilience is becoming increasingly popular in research on the ways people, families and communities recover from trauma, such as trauma from disasters, wars, or the loss of family members. A study of family resilience becomes important because the family is where people grow and develop. In addition, the family is the site of the main activity of the person so that the family become a quality determination of a person facing the future. To understand the process of family resilience, a multi system review is necessary in view of family conditions. The ecological perspective put forward by Urie Bronfenbrenner builds a model of interrelated relationships between families and between families and the social context.

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