Reproductive risk in mating between two translocation carriers: Case report and review of the literature
Kazushiro TsujiKouji NaraharaYuji YokoyamaShinsuke NinomiyaSuguru YonesawaYuji HiramatsuH MasaokaNaofumi KudoYoshiki Seino
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Abstract We conducted a study to determine the reproductive risk in a couple who were translocation carriers. This couple, who carried balanced reciprocal translocations, experienced habitual abortions. The wife had a karyotype of 46,XX,t(7;13)(p15.3;q12.3) and the husband of 46,XY,t(1;7)(p11.1;p11.1). Chromosome study of their fourth abortus demonstrated a chimera consisting of two cell lines with a 46,XY and a 46,XX,t(1;7)(p11.1;p11.1)pat, −13, +der(7)t(7;13)(15.3;q12.3)mat, karyotype. A review of the literature indicates that the risk of having unbalanced live offspring or of spontaneous abortion/stillborns is similar in couples in whom both were translocation carriers and in couples in whom one individual was a translocation carrier. The apparent lack of increased reproductive failure may result from the selective disadvantage of aneusomic gametes at fertilization or very early spontaneous abortions of unbalanced conceptuses. © 1993 Wiley‐Liss, Inc.Keywords:
Proband
Robertsonian translocation
Gamete
Abstract Background Joint hypermobility (JH) is used to define the capability of a joint moving passively or actively beyond normal limits along physiological axes, which can be influenced by multiple factors (genetic factors, age, gender, weight and training), and the accurate incidence is unclear. In this study, we aimed to identify the genetic cause of JH in 15 patients from seven unrelated Chinese families. Results We identified seven pathogenic/likely-pathogenic variants: two novel mutations, in the COL6A2 and CHST14 genes, and five reported mutations in the COL11A1 , NALCN , GALNS and COL5A1 respectively. Based on the genetic testing, we were able to diagnose the precise condition for each patient: Stickler syndrome in Proband 1, the Ullrich congenital muscular dystrophy in proband 2, CLIFAHDD syndrome in proband 3, Mucopolysaccharidosis IVA in proband 4, Classical Ehlers-Danlos syndrome (EDS) in proband 5, and Musculocontractural EDS in proband 6. Moreover, this is the first time to describe the Musculocontractural EDS caused by CHST14 in China. Though the expression of the mRNA and protein have not significantly changed, we speculated that the mutation of the CHST14 may affect the sulfotransterase activity of the protein. Conclusions The diagnosis in all probands except proband 6 and 7 were corrected following genetic analysis, indicating the importance of the genetic testing in the diagnosis and classification of JH cases. Our findings also offered insight into the genotype-phenotypes relationship and expanded the mutation spectrum of the disease-causing genes in JH.
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Joint hypermobility
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The data consists of sixty probands affected with Retinitis pigmentosa. Syndromic cases were found in five percent of the RP probands. Segregation analysis was carried out on proband sibship data. The ascertainment probability was estimated at 0.5517. Analysis of the data by parental mating types of proband sibships indicated the presence of dominant forms of RP (2.05%). Analysis of proband sibships indicated the presence of low risk families in the Normal x Normal matings (45%) and in the consanguineous matings (40%). The hypothesis of recessive inheritance could be confirmed only in multiplex sibships (p = 0.383 +/- 0.0793). Data on proband matings though incomplete conformed in general to autosomal recessive gene hypothesis.
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Pedigree chart
Inheritance
Autosomal recessive inheritance
Consanguineous Marriage
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Among 6800 consecutive blood samples studied for clinical cytogenetic diagnosis, we identified 30 families in which one parent of the proband had a balanced reciprocal autosomal translocation (excluding Robertsonian rearrangements). Twenty-eight of the 30 families had a malformed and/or mentally retarded proband: 19 with an unbalanced derived chromosome, 3 with abnormalities involving chromosomes other than those in the translocation, 5 with a "balanced" reciprocal translocation, and 1 with a normal karyotype. We hypothesize that the latter 6 affected probands with "balanced" karyotypes could be abnormal due to submicroscopic deletions and duplications as was originally suggested by Jacobs [1984]. Particularly in these 6 families, 83% of translocation breakpoints were associated with fragile sites, more than expected by chance (P < 0.025). This supports the report of an association between fragile sites and constitutional chromosome breakpoints by Hecht and Hecht [1984]. To explain these findings, we propose that autosomal fragile sites are unstable areas which predispose to breaks and unequal crossing over near the fragile site breakpoints creating minute duplications and deletions. Consequently, newborn infants inheriting a seemingly "balanced" karyotype from a normal parent with a balanced reciprocal translocation may still be at an increased risk of being malformed and/or developmentally delayed because of submicroscopic chromosomal imbalances.
Proband
Breakpoint
Chromosomal rearrangement
Robertsonian translocation
Chromosomal fragile site
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Robertsonian translocation
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The gene mutation and clinical characteristics of a patient with non-classical 21-hydroxylase deficiency and his family were analyzed.A patient was diagnosed with non-classical 21-hydroxylase deficiency in the Department of Endocrinology of People's Hospital of Xinjiang Uygur Autonomous Region in December 2016. The clinical data and related gene-sequencing results were analyzed. The detected mutations were verified in nine members of the family.Gene-sequencing results revealed that the proband and the other three members of the family (proband, proband's mother's younger brother and the proband's mother's younger brother's younger daughter, and proband's second elder sister) shared the following mutations: Ile173Asn, Ile237Asn, Val238Glu, Met240Lys, Val282Leu, Leu308Phefs*6, Gln319Ter, Arg357Trp, and Arg484Profs. The Val282Leu mutation was heterozygous in the proband's mother's younger brother's younger daughter, but homozygous in the other three individuals. The father of the proband, the elder brother of the father of the proband, the third younger brother of the father of the proband, and the elder sister of the proband all carried only the Val282Leu mutation.Val282Leu is the gene responsible for non-classical 21-hydroxylase deficiency. Screening for this gene in the offspring of patients with non-classical 21-hydroxylase deficiency may help to identify cases early.
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Daughter
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The paper presents a clinical and genealogical characterization of 50 probands suffering from coronary heart disease concurrent with various lipid metabolic disturbances and 211 first-degree relatives whose data have been obtained from the probands' histories while making up their pedigrees. The prevalence of atherosclerosis among the first-degree relatives has been demonstrated to be related to the nature of lipid metabolic disturbances in a proband. Some dyslipoproteinemias in the proband have been characterized by early onset of coronary heart disease, stroke, and their grave course in close relatives.
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Objective To investigate the genealogical tree of women with Becker muscular dystrophy (BMD).Methods Creatine phosphate kinase(CK), hydroxybutyric dehydrogenase and lactic hydrogenase were determined by selective suppression test, and myohemoglobin was detected by ELISA.DNA from the family members was assayed by PCR and the amplified fragment length polymorphism by silver staining method.Results CK of proband′s mother was above normal.CK and myohemoglobin of proband and his two young sisters were much higher than normal.MP1P 5′CA44 and 49 fragments of proband′s mother from family 1(I2) were heterozygous.Heterozygous fragment wasn′t found in proband′s DNA.Intron 5′CA45 of proband′s two young sisters(II2, II3) was heterozygous.Conclution Proband′s mother is a carrier with abnormal gene of BMD, proband′s father and mother are consanguineous marriage and passed the pathogenic gene to proband and their two daughters.Therefore their son and two daughters are patients with BMD.
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Objective:To explore the distribution of various karyotypes of Robertsonian translocation carriers among the Chinese population receiving genetic consultation,analyze the effect of Robertsonian translocation on reproduction and individual clinical development,calculate the sex ratios of Robertsonian translocation carriers and the cases with trisomy 21 of Robertsonian translocation. Methods:G-banding technique was used for karyotype analysis of lymphocytes in peripheral blood.896 Robertsonian translocation carriers and the cases with trisomy 21 of Robertsonian translocation in China reported by CNKI database from 1999 to 2008 were accumulated,the data of karyotype distribution were analyzed statistically. Results:Among 3 921 cases receiving genetic consultation,30 cases were diagnosed as Robertsonian translocation carriers and 6 cases were diagnosed with trisomy 21 of Robertsonian translocation.It was found that the distribution of Robertsonian translocation types was not random,the proportions of rob(13q14q)(43.14 %) and rob(14q21q)(18.55%) of Robertsonian translocation carriers were higher than those of cases with other Robertsonian translocation types;among the cases with Down's syndrome of translocation type,the proportions of rob(14q21q)(51.93%) and rob(21q21q)(26.61%) were higher than those of cases with other types.There was significant difference in sex ratio between the patients with Robertsonian translocation and normal population,the sex ratio was 0.52 in Robertsonian translocations carriers,and the sex ratio was 1.72 in cases with trisomy 21 of translocation.The reproductive conditions of 157 Robertsonian translocations carriers were analyzed,the average abortion rate was 99.31% when one of the couples was homologous Robertsonian translocations carriers,the mean times of abortion was 4.21;the average abortion rate was 84.36% when one of the couples was nonhomologous Robertsonian translocations carriers,the mean times of abortion was 2.36.The clinical manifestations of Robertsonian translocations carriers included primary and secondary amenorrhea,infertility,poor development of secondary sexual characteristics,hypophrenia and azoospermia besides of recurrent abortion,fetal development arrest. Conclusion:Robertsonian translocation is one of the major genetic causes of recurrent abortion and infants with trisomy 21 of translocation;the individuals with different karyotypes of Robertsonian translocation have significant difference,which should be treated differentially during genetic consultation.
Robertsonian translocation
Trisomy
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Data from 206 pairs of nuclear family members were analyzed to study the influence of genetic factors on the occurrence of chronic obstructive pulmonary disease (COPD) and its familial aggregation. Results showed that occurrence of COPD appeared in family aggregation. Risk of occurrence of COPD in the relatives (father, mother, brothers and sisters) of the proband with COPD increased by 2.07 times, as compared with relatives of the controls. Significant differences of the risk of COPD in fathers, brothers and sisters between proband and controls were observed, but not in mothers. It suggests relatives of the proband are more susceptible to COPD than those of the controls, and genetic factor may contribute to pathogenesis of COPD.
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Family aggregation
Pathogenesis
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A pedigree is described where the proband affected by hemophilia A, as well as his healthy brother, have died (so that their DNA was not available for analysis), and yet, the determination of five linked RFLPs in the remaining pedigree members made it possible to ascertain the carrier status in the proband's grand-daughter. (Fig. 1, Tab. 1, Ref. 16).
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Daughter
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