An oculocerebral hypopigmentation syndrome: a case report with clinical, histochemical, and ultrastructural findings.

A 4 year old boy is reported with tyrosinase positive hypopigmentation, mental retardation, ataxia, and myopia. Radiological investigation showed occipital cerebral atrophy, coxa valga, and generalised osteoporosis. The skin histology and electron microscopy are reported and discussed. The clinical features are similar to those of the oculocerebral hypopigmentation syndrome described by Preus et al.     

X-linked congenital ataxia: a new locus maps to Xq25-q27.1

We report clinical and molecular studies on a large American family of Norwegian descent with X-linked nonprogressive congenital ataxia (XCA) in six affected males over three generations. Neuroimaging showed global cerebellar hypoplasia without evidence of supratentorial anomalies. Linkage analysis resulted in a maximum LOD score Z = 3.44 for marker DXS1192 at Theta = 0.0 with flanking markers DXS1047 and DXS1227 defining a region of 12 cM in Xq25-q27.1. The clinical and neuroradiological findings in the present family are very similar to those described in two reported X-linked families [Illarioshkin et al., 1996; Bertini et al., 2000]; however, the newly identified locus does not overlap with the one defined previously, indicating that there are at least two genes responsible for this rare form of X-linked congenital cerebellar ataxia with normal intelligence.     

AT-related disorder

Two sisters with a complex clinical pattern, including microcephaly, microgenia, defects of skin pigmentation, anal stenosis/atresia, and combined immunodeficiency together with spontaneous chromosomal instability and cellular hypersensitivity to X-rays and bleomycin are described. Complementation studies on heterokaryons proved that the underlying genetic defect is non-allelic with that of patients with ataxia telangiectasia (complementation groups AB-E) and the Nijmegen breakage syndrome, but identical with the case described by Conley et al. (1986).     

中国汉族人群脊髓小脑性共济失调1、2、3、6、7、8、10、12、17亚型和齿状核红核苍白球路易体萎缩亚型多核苷酸正常重复次数范围研究

目的 研究中国汉族健康人群中脊髓小脑性共济失调(spinocerebellar ataxias,SCA)1、2、3、6、7、8、10、12、17亚型和齿状核红核苍白球路易体萎缩(dentatorubral-pallidoluysian atrophy,DRPLA)亚型致病基因多核苷酸正常重复次数的范围,以助于SCA各亚型基因诊断平台的建立和诊断标准的确认.方法 应用荧光聚合酶链反应、毛细管凝胶电泳等技术对300名健康个体进行SCA 1、2、3、6、7、8、10、12、17亚型和DRPLA亚型致病基因多核苷酸正常重复次数的检测分析.结果 在300名健康个体中CAG三核苷酸在SCA1亚型中为17～35次,在SCA2亚型中为14～28次,在脊髓小脑性共济失调3型/Machado-Joseph病,SCA3/Machado-Joseph disease,SCA3/MJD亚型中为13～41次,在SCA6亚型中为4～16次,在SCA7亚型中为5～17次,在SCA12亚型中为5～21次,在SCA17亚型中为23～41次,在DRPLA亚型中为12～33次;在SCA8亚型中CTA/CTG三核苷酸的重复次数为12～43次;在SCA10亚型中ATTCT五核苷酸的重复次数为9～32次.其中SCA8的12次CTA/CTG三核苷酸重复,SCA10的9次ATTCT五核苷酸重复,SCA17的23次CAG三核苷酸重复,为目前国内外报道的3种亚型多核苷酸正常重复次数的最小次数.SCA3/MJD亚型的41次CAG三核苷酸重复,SCA10亚型的32次ATTCT五核苷酸重复为目前报道的2种亚型多核苷酸正常重复次数的最大次数.结论 SCA各亚型多核苷酸正常次数范围存在种族差异,与遗传和种族背景相关;首次建立了中国汉族人群10种不同SCA亚型正常核苷酸重复次数范围,可为SCA的诊断提供参考标准.     

HLA—Determination in Families with Hereditary Ataxia

In three families with hereditary ataxia, where the inheritance pattern was autosomal and dominant, HLA antigens were determined in 25 members. In two of the families, HLA linkage of disease was suggested, whereas in the third family, the data did not directly support this concept, since two recombinational events between the postulated locus for disease and the HLA region had to be assumed. However, with this assumption, our data are compatible with those of one family described recently (Jackson et al. 1977) implying the presence on the sixth chromosome, outside the HLA region, of a locus that determines the development of spino cerebellar ataxia (SCA). Further tests with definition of enzyme markers will have to be performed before conclusions as to HLA linkage of a postulated SCA gene can be made.     

Screening for FMR-1 premutations in 122 older Flemish males presenting with ataxia

Recently, Hagerman et al described the occurrence of a late-onset neurological disorder in five male carriers of the fragile-X (FMR-1) premutation. The major characteristics of this disorder, designated the Fragile-X Tremor Ataxia Syndrome (FXTAS), are progressive intention tremor, cerebellar ataxia and cognitive decline. Most cases of FXTAS published thus far were ascertained through families with a known fragile-X proband. Since cerebellar ataxia is one of the main cardinal features, we performed FMR-1 premutation screening in 122 male patients, older than 50 years, who were referred to us for testing of the spinocerebellar ataxia (SCA 1, 2, 3, 6, 7) genes and who were found to be negative. In this group of patients, we found five patients with an FMR-1 premutation. In four of them, a definite diagnosis of FXTAS could be made, based on the proposed diagnostic clinical and radiological criteria for FXTAS. In light of these figures, we recommend that FMR-1 analysis should be included in the molecular diagnostic work-up in the group of male ataxia patients older than 50 years.     

Unraveling the genetic and molecular basis of posterior column ataxia and retinitis pigmentosa

Mutations in FLVCR1 cause posterior column ataxia and retinitis pigmentosa Rajadhyaksha et al. (2010) American Journal of Human Genetics 87:643–654     

Yet another gene mutation: dysfunction in mitochondrial protein quality control causing hereditary ataxia

Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28. Di Bella et al. (2010) Nature Genetics 42(4): 313–321     

Cherubism, gingival fibromatosis, epilepsy, and mental deficiency (Ramon syndrome) with juvenile rheumatoid arthritis

This is a report on four persons in one family with a condition similar to that described by Ramon et al [Oral Surg 24:436-48, 1967] in two sibs born to a consanguineous couple. Our patients also had mental deficiency, epilepsy, cherubism due to fibrous dysplasia of the maxillae, gingival fibromatosis, hypertrichosis, and stunted growth. This appears to be an autosomal recessive trait in both families. Our patients are the second set reported with this syndrome; they also have juvenile rheumatoid arthritis, which was not described in the family reported by Ramon et al [Oral Surg 24:436-48, 1967]. We conclude that the Ramon syndrome should also include juvenile rheumatoid arthritis.     

Additional case of Tsukahara's syndrome or new syndrome: further delineation of the association of microcephaly and radio-ulnar synostosis

In 1994, Giuffré et al. reported two unrelated families in which some of the members had microcephaly and radio-ulnar synostosis, suggesting a new condition. Since this first report, Tsukahara et al. and Udler et al. described two distinct patients with a different condition characterized by radio-ulnar synostosis, short stature, microcephaly, scoliosis, and mental retardation. Here we report on a new case of microcephaly and radio-ulnar synostosis and discuss the possible relationship between Tsukahara's syndrome and the phenotype described by Giuffré et al.     

From Ag phenotyping to molecular genetics: apolipoprotein B, serum lipid levels and coronary artery disease in Finland

The Ag polymorphisms of low density lipoproteins (LDL) were described in the 1960's (Allison & Blumberg 1961, Bütler 1967). The first report suggesting that they may be associated with serum lipid levels did not appear until 1976 (Berg et al. 1976). Out of the 10 populations studied, the Finnish population showed the most marked association between Ag(x —) phenotype and elevated serum cholesterol and triglyceride levels. After this, little progress was made for several years, possibly because Ag antibodies were available in very few laboratories. The introduction of monoclonal antibodies directed against apo B in the 1980's provided a novel means to detect immunophenotypes of LDL (for review, see Tikkanen 1987a,b). Later on, the associations between common DNA polymorphisms of apo B, and the immunogenetic polymorphisms detected with Ag and monoclonal antibodies were described (Berg et al. 1986, Ma et al. 1987, Ma et al. 1989, Wang et al. 1990. Xu et al. 1989, Dunning et al. 1991). Some of the studies carried out in Finland demonstrated associations between certain apo B polymorphisms and serum lipid levels, while some associations reported elsewhere were absent in Finnish individuals. We explored the possibility that variation at the apo B gene locus contributed to the common occurrence of hyperlipidemias and coronary heart disease (CHD) among the Finns.     

Ectodermal dysplasia, lipoatrophy, diabetes mellitus, and amastia: a second case of the AREDYLD syndrome.

A 19-year-old female with ectodermal dysplasia, lipoatrophy, diabetes mellitus, and amastia is described. This complex of symptoms is very similar to that of a case published by Pinheiro et al [1983] under the acronym of AREDYLD syndrome.     

Microcephaly, seizures, genital hypoplasia, and abnormalities of the hands and feet in a 4-year-old boy with possible Wiedemann syndrome

We report on a 4-year-old boy with short stature, microcephaly, BNS ( Blitz-Nick -Salaam) seizures, and global developmental delay. In addition, small and fleshy hands and feet as well as hypoplastic scrotum and testes were observed. The clinical features of the patient are compared with the patients previously described by Wiedemann et al. and Nevin et al. They reported three patients with a syndrome characterized by short stature, microcephaly, global developmental delay, abnormalities of hands and feet, seizures, large anterior fontanelle, scrotal hypoplasia, micropenis, cryptorchism, urinary tract abnormalities, and inguinal hernia (Wiedemann syndrome).     

Syndrome of congenital cataracts, sensorineural deafness, Down syndrome-like facial appearance, short stature, and mental retardation: two additional cases

An apparently new syndrome of congenital cataracts, sensorineural deafness, Down syndrome-like facial appearance, short stature, and mental retardation was described by Gripp et al. 1996. The authors reported on two unrelated patients with congenital cataracts, sensorineural deafness, distinctive facial appearance, mental retardation, postnatal short stature, and skeletal changes. We report on two additional patients with findings most similar to the reported patients by Gripp et al. 1996, including bilateral congenital cataracts, hearing loss, craniofacial abnormalities, short stature, skeletal abnormalities, and developmental delay. Both of the patients reported herein had chromosome microarray analysis, which showed normal results in Patient 2 but abnormal results in Patient 1 and his mother who both had a chromosome 11q25 subtelomere deletion. Patient 1 and his mother's findings are atypical for the common findings reported in Jacobsen syndrome (11q terminal deletion syndrome), and consistent with the patients reported by Gripp et al. 1996. The etiology for these cases has been unknown. The microarray results on Patient 1 suggest that the other patients with findings of developmental delay, short stature, congenital cataracts, sensorineural hearing loss, and similar craniofacial features may have either a microdeletion of chromosome 11q terminal region or haploinsufficiency of a gene localized to this region.     

The Meier-Gorlin syndrome, or ear-patella-short stature syndrome, in sibs

The Meier-Gorlin syndrome, first described by Meier and Rothschild [1959: Helv Paediatr Acta 14:213-216] and further delineated by Gorlin et al. [1975: A Selected Miscellany, p 39-50], is characterized by short stature, slender body build, craniofacial anomalies, microtia, delayed skeletal development, hypogonadism, and absence of the patellae. It has also been called the ear-patella-short stature syndrome [Boles et al., 1994: Clin Dysmorphol 3:207-214]. We report on two brothers with Meier-Gorlin syndrome, the younger of whom was more severely affected. Both patients had severe deafness and congenital labyrinthine anomalies, which have not previously been described as features of this syndrome. The neuromotor and mental development of these patients was adversely affected by late diagnosis, deafness, and their sociocultural environment, but their cognitive ability fell within the range observed in other Meier-Gorlin patients. Neuroradiographic imaging and functional inner ear investigations are recommended in the diagnostic workup of this rather specific, probably autosomal recessive mental retardation syndrome with multiple congenital anomalies.     

Spinocerebellar ataxia,hypogonadotropic hypogonadism,and choroidal dystrophy (Boucher-Neuhäuser syndrome

We describe two families (including one previously reported) in which cerebellar or spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy result from abnormal function of an autosomal recessive gene. Review of the literature adds one other family with this disorder. These three examples confirm the existence of this triad as a specific, pleiotropic, single-gene syndrome. Careful ophthalmologic evaluation of patients with ataxia and hypogonadotropic hypogonadism may identify additional cases.     

Female external genitalia, absent uterus, and probable agonadism in a 46,XY infant with bilateral upper amelia

This report describes a 46,XY phenotypic female infant with absent uterus, probable agonadism, and bilateral upper amelia. The constellation of anomalies is similar to that of the patient described by Temocin et al. (Acta Paediatr Jpn 1997: 39: 631–633), and may suggest a developmental link between genital region and upper limbs.     

Low threshold facilitation of inspiration by lung volume increments

Vagally mediated, volume dependent excitatory effects on phrenic nerve activity have been recently described in anesthetized dogs and pigs, but could not be ascertained in rabbits and baboons (Bartoli et al. 1975, Huszczuk et al. 1977, Cross et al. 1980, Karczewski et al. 1980). Results presented here on cats confirm and further characterize a volume dependent facilitatory effect on inspiratory intercostal and phrenic activity in this species.     

Spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy (Boucher-Neuh?user syndrome)

We describe two families (including one previously reported) in which cerebellar or spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy result from abnormal function of an autosomal recessive gene. Review of the literature adds one other family with this disorder. These three examples confirm the existence of this traid as a specific, pleiotropic, single-gene syndrome. Careful ophthalmologic evaluation of patients with ataxia and hypogonadotropic hypogonadism may identify additional cases.