下肢静脉曲张的遗传分析

目的对本院１９９１～１９９６年门诊及住院的下肢静脉曲张（ＶＶＬＥ）患者６８个家系的遗传方式、男女患者比及传递的方式进行研究，以探讨该病的遗传学特点。方法用Ｗｅｉｎｂｅｒｇ的先证者法计算确认概率π；用分离分析计算机程序计算分离比Ｐ和散发病例比例Ｘ。结果３种婚配型Ｕ×Ｕ、Ｕ×Ａ和Ａ×Ａ混合分析及Ｕ×Ａ、Ｕ×Ｕ多发家庭分别分析，ＶＶＬＥ均为常染色体显性遗传，不完全外显，外显率分别为９１．９４％、７８．１４％和６９．９２％，混合分析散发病例比例为２４．３２％；Ｕ×Ｕ总体分析，ＶＶＬＥ为常染色体隐性遗传，散发病例比例为３６．７５％。结论ＶＶＬＥ主要为迟发性常染色体显性遗传，不完全外显。Ｕ×Ｕ婚配型为常染色体隐性遗传，患者比例为男女＝２．３９１，男性女性均有传递给后代的可能     

非特异性精神发育迟滞的遗传异质性

目的　探讨非特异性精神发育迟滞 (non- specific mental retardation,NSMR)的遗传方式。方法　采用分离分析法、Finney法和 Falconer法 ,对山东省遗传病群体调查中筛选出的 15 7个 NSMR家系进行了研究。结果　 U×U多发家庭接受常染色体隐性遗传 ;U× U总体属于常染色体隐性遗传 ,同时还有多基因的主基因效应 ,散发病例为 46 % ;U× A符合常染色体显性遗传 ,不完全外显。结论　 NSMR的遗传方式具有遗传异质性     

328例非特异性精神发育迟滞的隐性基因分析

采用分离分析和血缘分析方法，对山东省遗传病调查中发现的３２８个父母双方均正常的中、重度非特异性精神发育迟滞（ＮＳＭＲ）家系进行了分析。结果表明，多发家庭先证者的平均近婚系数显著高于一般群体，分离比接近０．２５。提示隐性基因在中、重度ＮＳＭＲ发生中起一定作用。在重度ＮＳＭＲ，散发病例占４０．７％，Ｘ连锁隐性遗传占９．１２％，常染色体隐性遗传占５０．１８％。常染色体隐性基因位点数的最小估计值为２４，各位点的平均基因频率为０．００３５，携带者总频率为１７．５４％；在中度ＮＳＭＲ，散发病例占６１．５％，Ｘ连锁隐性遗传占１１．５３％，常染色体隐性遗传占２６．９７％，常染色体隐性基因位点数的最小估计值为１３２，各位点的平均基因频率为０．００２１，携带者总额率为５４．９５％。     

病理性近视眼的遗传流行病学研究

目的 对上海市眼耳鼻喉科医院病理性近视眼患者６２个家系的遗传方式进行研究,探讨可能的遗传模式。方法 用ＳＥＧＲＡＮＢ软件进行简单分离分析,计算确认概率π,并在此基础上计算分离比ｐ和散发概率ｘ,用ＳＡＧＥ－ＲＥＧＤ软件进行复合分离分析,探讨可能的遗传模式和致病基因概率。结果 婚配类型为Ｎ＊Ｎ的家系表现为常染色体隐性遗传,Ａ＊Ｎ婚配类型则可能为隐性遗传模式（不能排除显性遗传模式）,两种婚配类型中均在一     

家族性自发性气胸

本文分析我院１９８０－１９９０年共收治的自发性气胸１４３例，其中发现Ａ（李家），Ｂ（刘家），Ｃ（马家）三家系１２例病人罹患此病。认为本病具有家族聚集现象。通过家系调查和系谱分析指示家族性自发性气胸的遗传方式属于常染色体显性遗传、常染色体隐性遗传和Ｘ连锁遗传。     

原发性高血压遗传流行病学研究

目的探讨原发性高血压的遗传模式。方法对117个原发性高血压家系用分离分析法和多基因阈值理论进行遗传模式的研究。结果常染色体显性遗传和隐性遗传模式的统计学检验均具有显著意义（P〈0.05）;资料中子女高血压发病情况分析显示,此病不符合性连锁遗传方式;多基因阈值分析的遗传率为74.83%。结论原发性高血压为多基因遗传疾病,平均遗传度为74.83%±4.28%,对有遗传易感性人群应重点管理,加强防治。     

系统性红斑狼疮遗传方式的分析

为探讨系统性红斑狼疮（ＳＬＥ）的遗传方式，对２２０例ＳＬＥ家系资料作了分析。结果６．８％的患者有红斑狼疮家族史，分离比为０．０２１３７，不符合单基因遗传；遗传度为５７％±７．５％。患者出生顺序在第５胎次以上较多并接近显著，提示ＳＬＥ的发病可能与遗传和环境有关。用Ａ类回归Ｌｏｇｉｓｔｉｃ模型进行复合分离分析，结果拒绝单纯环境模型、显性模型和无传递模型，接受主基因模型、隐性模型和共显性模型。提示单纯环境不能完全解释ＳＬＥ的发病，ＳＬＥ存在上下代的传递，可能有多主基因效应，这些主基因可能为隐性和／或共显性遗传。另外，劳累、病毒感染、日晒、寒冷刺激等可能是发病的诱因。以上均提示ＳＬＥ是一种多因子遗传病。     

Wilson病临床生化遗传分析(附15例报告)

本文通过临床及生化检查确诊15例Wilson病（脑型）。个别病例伴骨和肝脏损害。经采用青霉胺为主结合控制饮食，收到较好的效果。本级病例中14例为散发。遗传方式常染色体隐性遗传。仅1例，有家族史，支持常染色体显性遗传的可能。     

301例精神分裂症家系非配对对照调查

本文通过对301例精神分裂症和272个正常人家系的非配对对照分析表明:阳性家族史率,病例组明显高于对照组。各级亲属患病率均高于群体,亲属与患者血缘关系越近患病率越高,特别是精神分裂症的患病率高低与血缘关系近远显著相关。其遗传方式既不符合常染色体单基因显性和隐性遗传,也不符合性连锁遗传,而与多基因遗传相符。其加权平均遗传率为70.27％。     

Wilson病临床生化遗传分析

本文通过临床及生化检查确诊１５例Ｗｉｌｓｏｎ病（脑型）。个别病例伴骨和肝脏损害。经采用青霉胺为主结合控制饮食，收到较好的效果。本组病例中１４例为散发。遗传方式常染色体隐性遗传。仅１例，有家族史，支持常染色体显性遗传的可能。     

The inheritance of juvenile onset primary open angle glaucoma

Juvenile onset open angle glaucoma (JOAG) affects patients before 40 years of age, who present with high intraocular pressure and deep steep cupping of the optic nerve head. While it was considered to be inherited in an autosomal dominant fashion, recent studies have shown an autosomal recessive pattern as well as sporadic occurrence of the disease in several families. In this review, we analyze the genetic basis of the disease along with common mutations and their association with JOAG. We also analyzed the inheritance patterns in a large group of unrelated JOAG patients (n = 336) from Northern India wherein the prevalence of familial occurrence was assessed and segregation analysis performed, to determine the mode of inheritance.     

Genetic and segregation analysis of congenital cataract in the Indian population

Congenital cataract is a major cause of blindness in children, and there is wide variation in the few reports available on the frequencies of its different inheritance patterns. Two hundred and fifty-two families with congenital cataract belonging to 13 different states of India, were clinically and genetically investigated to study their inheritance and segregation patterns. Twenty-one percent of the cases were autosomal recessive, 15% autosomal dominant, 63% were simplex cases, and in the remaining cases the inheritance pattern was not clear. A high incidence of consanguinity (50.9%) was observed in autosomal recessive cases. Out of 340 affected individuals, 222 (65.3%) were males and 118 (34.7%) were females. Segregation analysis showed good agreement in autosomal dominant and recessive families and the data are indicative of the prevalence rate for different inheritance patterns of congenital cataract within the Indian population.     

Family trio-based sequencing in 404 sporadic bilateral hearing loss patients discovers recessive and De novo genetic variants in multiple ways

Hereditary hearing loss (HL) has high genetic and phenotypical heterogeneity including the overlapping and variable phenotypic features. For sporadic HL without a family history, it is more difficult to indicate the contribution of genetic factors to define a pattern of inheritance. We assessed the contribution of genetic variants and patterns of inheritance by a family trio-based sequencing and provided new insight into genetics. We conducted an analysis of data from unrelated sporadic patients with HL (n = 404) who underwent trio-based whole-exome sequencing (trio-WES) or proband-only WES (p-WES) or targeted exome sequencing (TES), and the samples of their unaffected-parents (n = 808)were validated. A molecular diagnosis was rendered for 191 of 404 sporadic HL patients (47.3%) in multiple modes of inheritance, including autosomal recessive (AR), autosomal dominant (AD) caused by de novo variants, copy-number variants (CNVs), X-linked recessive, and dual genetic diagnosis. Among these patients, 83 (43.5%) cases were diagnosed with variants in rare genes. Sporadic HL patients were identified by multiple modes of transmission. Observed variations in rare genes and multiple modes of inheritance can strikingly emphasize the important etiological contribution of recessive and de novo genetic variants to a large cohort of sporadic HL cases plus their parents.     

Inheritance pattern of Beckwith-Wiedemann syndrome is heterogeneous in 291 families with an affected proband

Beckwith-Wiedemann syndrome (BWS) is congenital disorder whose molecular etiology is related to genetic and epigenetic mutations on 11p15. The majority of cases of BWS are sporadic, but a substantial proportion are familial, with an unknown inheritance pattern, although autosomal dominant and sex-dependent inheritance have been proposed. We tested the hypothesis that in familial BWS, autosomal dominant inheritance is the primary mode of transmission underlying familial instances. Segregation analysis was performed in 291 families ascertained with an affected child. Individuals were considered to have BWS if they had two of five major features: macroglossia, macrosomia, hypoglycemia at birth, abdominal wall defect, and ear pits or creases. Models of inheritance were tested using pedigree analysis package (PAP) parameterized for a discrete trait. A total of 291 families of an affected proband were included in the study. The analysis was based on a revised general model that included a boundary solution. Sporadic and environmental models were rejected. Overall, the results suggested Mendelian inheritance but under recessive or additive mode of inheritance, which fit the data equally well rather than dominant inheritance. However, the presence of families in the cohort consistent with dominant and sex-dependent inheritance suggest familial BWS may be a heterogeneous group comprised of different inheritance patterns. Familial BWS does not appear to be consistent with autosomal dominant transmission, and is likely a complex mixture of different inheritance patterns.     

Possible autosomal-recessive ocular coloboma

Ocular coloboma as an isolated anomaly often is inherited as an autosomal dominant trait. Possible autosomal recessive inheritance is suggested by the presence of colobomatous malformations in a brother and sister whose parents have apparently normal eyes. Possible genetic heterogeneity of isolated ocular coloboma makes genetic counseling in sporadic cases difficult since cases may be due to autosomal dominant and autosomal recessive mutations and non-genetic causes.     

Reply to Dr. Winter

Although Costello syndrome is considered to be an autosomal recessive disorder, review of 20 families demonstrated that the 37 sibs of the probands were all normal. In 6 families on whom pedigrees were not available, 2 affected sib-pairs were born. Even if there were no normal offspring in these latter families, the occurrence of the Costello syndrome in only 2 of 39 sibs virtually excludes an autosomal recessive inheritance pattern (P = 0.999). Moreover, a significant increase of mean paternal age (38.0 yr) and paternal-maternal age difference (7.36 yr) suggests sporadic autosomal dominant mutations as a likely cause. The 2 reported cases of affected sibs born to healthy parents may be explained by gonadal mosaicism, although heterogeneity with a small proportion of recessively inherited cases cannot be excluded. © 1994 Wiley-Liss, Inc.     

Segregation analysis of microcephaly

Microcephaly is a heterogeneous disorder with genetic and environmental causes. However, there is little information on what proportion of cases are caused by inherited susceptibility, or the mode of inheritance in familial cases. To address these questions, we have performed classical and complex segregation analyses for microcephaly on 2 sets of family data collected from genetic counseling clinics in Vancouver and Jerusalem. These samples consisted of 143 affected individuals in 127 families ascertained from Vancouver, and 101 affected individuals in 59 families ascertained from Jerusalem. The results of the segregation analyses for the Vancouver sample indicated that approximately half of all microcephaly cases were due to highly penetrant recessive mutant alleles, with the remainder being sporadic. Although a recessive model allowing for the occurrence of sporadic cases fit the data from Vancouver best, a dominant model could not be statistically rejected. The classical segregation analysis on the Jerusalem sample suggested that both a dominant model with 29% of the cases being sporadic and a purely recessive model provided adequate fit to the data. Although the complex segregation analysis of this sample indicated that a dominant model provided a more parsimonious explanation for the observed familial variation, a recessive model was only marginally rejected. It should be noted that in the Jerusalem sample, families tended to be ascertained in the genetic counseling clinic only after the birth of a second affected child. This could be a potential bias which could inflate the segregation ratio, thus giving the impression of dominant inheritance. Our analyses, while confirming the complex nature of the cause of microcephaly, indicate that it may be necessary to await the results of genetic linkage analysis before a definitive mode of inheritance can be determined. © 1996 Wiley-Liss, Inc.