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1.
SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature 总被引:3,自引:0,他引:3
Nanni L Ming JE Du Y Hall RK Aldred M Bankier A Muenke M 《American journal of medical genetics》2001,102(1):1-10
Solitary median maxillary central incisor (SMMCI) or single central incisor is a rare dental anomaly. It has been reported in holoprosencephaly (HPE) cases with severe facial anomalies or as a microform in autosomal dominant HPE (ADHPE). In our review of the literature, we note that SMMCI may also occur as an isolated finding or in association with other systemic abnormalities. These anomalies include short stature, pituitary insufficiency, microcephaly, choanal atresia, midnasal stenosis, and congenital nasal pyriform aperture stenosis. SMMCI can also be a feature of recognized syndromes or associations or a finding in patients with specific chromosomal abnormalities. We performed a molecular study on a cohort of 13 SMMCI patients who did not have HPE. We studied two genes, Sonic Hedgehog (SHH) and SIX3, in which mutations have been reported in patients showing SMMCI as part of the HPE spectrum. A new missense mutation in SHH (I111F), segregating in one SMMCI family, was identified. Our results suggest that this mutation may be specific for the SMMCI phenotype since it has not been found in the HPE population or in normal controls. Published 2001 Wiley-Liss, Inc. 相似文献
2.
Garavelli L Zanacca C Caselli G Banchini G Dubourg C David V Odent S Gurrieri F Neri G 《American journal of medical genetics. Part A》2004,(1):93-95
Solitary median maxillary central incisor (SMMCI) is a rare dental anomaly. It is usually considered as a minor manifestation of holoprosencephaly (HPE). Some reported families had severe cases of HPE in some members and SMMCI in others. Mutations of Sonic Hedgehog (SHH) have been documented in these families. SMMCI has also been found as an isolated finding or together with other anomalies such as microcephaly, short stature, endocrine pathology, and choanal atresia. We describe a patient with SMMCI and a novel SHH mutation: Val332Ala. 相似文献
3.
Ribeiro LA Murray JC Richieri-Costa A 《American journal of medical genetics. Part A》2006,140(23):2584-2586
We report five Brazilian probands with PATCHED (PTCH) mutations and highly variable phenotypes with holoprosencephaly in four cases and holoprosencephaly-like facial features with a normal MRI in a fifth case. Three of our mutations were novel: Ala443Gly, Val751Gly, and Val908Gly. Two patients had the same mutation (Val908Gly), but were phenotypically different: alobar holoprosencephaly, absent nasal septum, and midline cleft lip-palate in one case, and lobar holoprosencephaly, macrocephaly, hypertelorism, clefting of the nose, severe microphthalmia, and a single maxillary central incisor in the other. One of our patients had a Thr1052Met mutation, holoprosencephaly-like facial features, and a normal MRI. Ming et al. [(2002); Hum Genet 110:297-301] reported an identical mutation, but with alobar holoprosencephaly. 相似文献
4.
A holoprosencephalic female was born to a mother with a single central maxillary incisor. The newborn had microcephaly, hypotelorism, cebocephaly, palatoschisis, micrognathia, and normal chromosomes. Her brain computed tomography showed alobar holoprosencephaly. The mother was of normal intelligence and stature, and her brain computed tomography was normal. Other relatives did not have single central maxillary incisors, hypotelorism, or oral clefts. We show a further evidence of a single central maxillary incisor as an indicator of potential holoprosencephaly in the next generation, confirming an autosomal dominant trait with wide variety in penetrance and expressivity. 相似文献
5.
Marini M Cusano R De Biasio P Caroli F Lerone M Silengo M Ravazzolo R Seri M Camera G 《American journal of medical genetics. Part A》2003,(2):112-115
Holoprosencephaly (HPE) is the most common developmental defect of the forebrain and midface in humans, with a frequency of 1/16,000 live births. Different genes are implicated in the pathogenesis of HPE; these include SHH, ZIC2, SIX3, TGIF, and human DKK1. We describe here a family with recurrence of autosomal dominant HPE in different members showing a wide clinical variability. The mother presents a single central maxillary incisor and mild hypotelorism as signs of the diseases, while three of her sons were affected by HPE. By direct sequencing and restriction analysis of exon 2 of the SHH gene, we have identified a previously undescribed nonsense mutation at codon 128 (W128X). The identification of this mutation allowed us to give a prenatal diagnosis in this family and confirms a wide intrafamilial variability in the phenotypic spectrum. 相似文献
6.
Single central maxillary incisor and holoprosencephaly 总被引:3,自引:0,他引:3
H Hattori T Okuno T Momoi K Kataoka H Mikawa K Shiota 《American journal of medical genetics》1987,28(2):483-487
A holoprosencephalic child was born to a mother with a single central maxillary incisor. The infant had a median cleft lip, a flat nose with a single nostril, hypotelorism, and normal chromosomes. The head was brachycephalic and small, and computed tomography (CT) of the brain showed semilobar holoprosencephaly. The mother had mild hypotelorism but no anosmia, and her brain CT was normal. She was of normal intelligence and stature. Other relatives did not have single central maxillary incisors, hypotelorism, or oral clefts. Whether the mother's anomaly was a new mutation or had been inherited is unknown. We show the significance of a single central maxillary incisor as an indicator or potential holoprosencephaly in the next generation, even if other relatives are apparently normal. 相似文献
7.
Three patients--one with alobar holoprosencephaly and two with a holoprosencephaly-like phenotype--are reported with no identifiable mutations. In each case, one parent had a single maxillary central incisor (SMCI). We briefly review the holoprosencephaly-like phenotype and present a table of 25 conditions with SMCI. 相似文献
8.
Orioli IM Vieira AR Castilla EE Ming JE Muenke M 《American journal of medical genetics》2002,108(1):12-15
Oral clefts generally have a multifactorial etiology. A number of genes contribute to the formation of the face and palate. Cleft lip and/or palate can occur in pedigrees with autosomal dominant holoprosencephaly due to mutations in Sonic Hedgehog (SHH). In addition, animal models have shown that SHH is involved in face development. We thus examined the human SHH gene in 220 newborn infants with nonsyndromic oral clefts registered by the Estudio Colaborativo Latinoamericano de Malformaciones Congenitas: ECLAMC (Latin American Collaborative Study of Congenital Malformations). We found 15 variant bands in 13 patients with oral clefts, representing five different base changes, all of which were found by sequencing to represent silent polymorphisms. Four occurred in introns. The alteration occurring in an exon, Ser190Ser, may create a consensus sequence for the 3'splice site 6 bp downstream of the original consensus sequence. Thus, we did not identify any clearly disease-causing mutation in SHH in these patients, and conclude that SHH mutations are not a frequent cause of isolated oral clefts in humans. 相似文献
9.
Clinical molecular diagnostic centers routinely screen SHH, ZIC2, SIX3 and TGIF for mutations that can help to explain holoprosencephaly and related brain malformations. Here we report a prospective Sanger sequence analysis of 189 unrelated probands referred to our diagnostic lab for genetic testing. We identified 28 novel unique mutations in this group (15%) and no instances of deleterious mutations in two genes in the same subject. Our result extends that of other diagnostic centers and suggests that among the aggregate 475 prospectively sequenced holoprosencephaly probands there is negligible evidence for direct gene-gene interactions among these tested genes. We model the predictions of the observed mutation frequency in the context of the hypothesis that gene×gene interactions are a prerequisite for forebrain malformations, i.e. the "multiple-hit" hypothesis. We conclude that such a direct interaction would be expected to be rare and that more subtle genetic and environmental interactions are a better explanation for the clinically observed inter- and intra-familial variability. 相似文献
10.
Holoprosencephaly: a family showing dominant inheritance and variable expression. 总被引:2,自引:0,他引:2
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A family with probable dominant holoprosencephaly is presented with five affected subjects in two sibships, the offspring of healthy sisters who are presumed gene carriers. Of the affected children, three had cebocephaly and died shortly after birth. One had left choanal atresia, retinal coloboma, a single central maxillary incisor, microcephaly, short stature, and learning problems. Another had only a single central maxillary incisor. The occurrence of hypotelorism, microcephaly, and unilateral cleft lip and palate as minor manifestations of the gene in possible and probable gene carriers is discussed. 相似文献
11.
12.
A patient is described with a new association of microphthalmia, single central incisor, and hypopituitarism believed to represent a holoprosencephaly malformation. In view of the genetic ramifications of this malformation and its variable manifestations, we would like to alert the clinician to consider holoprosencephaly whenever midline malformations are detected. 相似文献
13.
14.
Roessler E; Belloni E; Gaudenz K; Vargas F; Scherer SW; Tsui LC; Muenke M 《Human molecular genetics》1997,6(11):1847-1853
Holoprosencephaly (HPE) is the most common brain anomaly in humans,
involving abnormal formation and septation of the developing central
nervous system. Among the heterogeneous causes of HPE, mutations in the
Sonic Hedgehog (SHH) gene have been shown to result in an autosomal
dominant form of the disorder. Here we describe a total of five different
mutations in the processing domain encoded by exon 3 of SHH in familial and
sporadic HPE. This is the first instance in humans where SHH mutations in
the domain responsible for autocatalytic cleavage and cholesterol
modification of the N-terminal signaling domain of the protein have been
observed.
相似文献
15.
Single mandibular incisor in a patient with del (18p) anomaly 总被引:2,自引:0,他引:2
A single mandibular incisor and an unusually narrow mandible and tongue were noted in an 8-year-old moderately retarded boy with 18p- (45, XY, der dic (18) (18qter-p11.2::22p 11.2-qter). While a single maxillary incisor, considered a minor feature of holoprosencephaly, was reported in three cases of 18p-, reduction of mandibular incisors has been a very rare finding and has never been noted in similar cases. 相似文献
16.
Shastry BS 《Journal of human genetics》2000,45(6):323-326
Incontinentia pigmenti (IP) is a rare disorder which affects organs and tissues of ectodermal and mesodermal origin. It is
characterized by swirled patterns of hyperpigmentation. In some cases, the condition is also associated with malformations
of the teeth, nails, skeleton, hair, eyes, and the central nervous system. The disorder is inherited as an X-linked dominant
trait and mostly affects females. However, there have been several cases of IP in males that survived to birth. While IP in
females could be caused by a skewed pattern of X-inactivation, three mechanisms: namely, the half-chromatid hypothesis, unstable
pre-mutation, and a higher rate of de-novo germline mutations, have been proposed to explain the survival of affected male
patients. Cytogenetic studies in several sporadic cases with signs similar to IP exhibited an X/autosomal translocation involving
a breakpoint at Xp11, suggesting a gene locus on Xp11 (IP1). Li
Received: August 15, 2000 / Accepted: August 30, 2000 相似文献
17.
Chong HJ Young NM Hu D Jeong J McMahon AP Hallgrimsson B Marcucio RS 《Developmental dynamics》2012,241(2):247-256
Background : The Frontonasal Ectodermal Zone (FEZ) is a signaling center in the face that expresses Sonic hedgehog (Shh) and regulates patterned growth of the upper jaw. Blocking SHH in the forebrain blocks Shh expression in the FEZ and creates malformations resembling holoprosencephaly (HPE), while inhibition of BMP signaling in the mesenchyme blocks FEZ formation and causes similar dysmorphology. Thus, the brain could regulate FEZ formation by SHH or BMP signaling, and if so, activating one of these pathways in the face might alleviate the effects of repression of SHH in the brain. Results : We blocked SHH signaling in the brain while adding SHH or BMP between the neural and facial ectoderm of the frontonasal process. When applied early, SHH restored Shh expression in the FEZ and significantly improved shape outcomes, which contrasts with our previous experiments that showed later SHH treatments have no effect. BMP‐soaked beads introduced early and late caused apoptosis that exacerbated malformations. Finally, removal of Smoothened from neural crest cells did not inhibit Shh expression in the FEZ. Conclusions : Collectively, this work suggests that a direct, time‐sensitive SHH signal from the brain is required for the later induction of Shh in the FEZ. We propose a testable model of FEZ activation and discuss signaling mediators that may regulate these interactions. Developmental Dynamics 241:247–256, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
18.
Schimmenti LA de la Cruz J Lewis RA Karkera JD Manligas GS Roessler E Muenke M 《American journal of medical genetics. Part A》2003,(3):215-221
Ocular (uveoretinal) colobomas occur in one in 10,000 individuals and present a substantive cause of congenital poor vision. The genetic bases of most forms of uveoretinal coloboma are elusive; mutations in PAX2 are found in only a few cases of coloboma of the retina and optic nerve that occur with renal anomalies as part of the renal-coloboma syndrome (MIM#120330; #167409). From experimental data that upstream expression of sonic hedgehog (SHH) controls Pax2 expression in mice and zebrafish, and from clinical experience that colobomas are observed frequently in patients with holoprosencephaly, we hypothesized that SHH could be a candidate for non-syndromic ocular colobomas (NSOC). We identified a three-generation family in which both a proband and his mother presented with iris and uveoretinal colobomas without optic nerve involvement. A novel 24 bp deletion in the gene SHH was identified in these affected family members, and cosegregated with the phenotype. This is the first report of the association of SHH mutations and uveoretinal coloboma. 相似文献
19.
Yang HC Shyur SD Huang LH Chang YC Wen DC Liang PH Lin MT 《Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand》2005,23(2-3):159-163
DiGeorge syndrome is a primary immunodeficiency disease characterized by dysgenesis of the thymus and parathyroid glands, conotruncal cardiac anomalies, and other dysmorphic features. Although most patients have a common microscopic deletion in chromosome 22q11.2, marked clinical variability exists. A solitary median maxillary central incisor (SMMCI) is a rare dental anomaly which may be an isolated occurrence or associated with congenital nasal airway abnormalities or holoprosencephaly. We report a patient with DiGeorge syndrome who was diagnosed at nearly 1 month of age and was later found to have a solitary median central incisor. Initially, the patient presented with recurrent episodes of respiratory distress attributed to partial airway obstruction, one of the phenotypic features of SMMCI. A fluorescence in situ hybridization study showed a chromosome 22q11.2 deletion. 相似文献
20.
Mark J. Stephan Kenneth L. Brooks Dan C. Moore Edward J. Coll Curt Goho 《American journal of medical genetics. Part A》1994,51(2):131-136
Oral-facial-digital syndrome (OFDS) type VI (Váradi syndrome) is an autosomal recessive trait of orofacial anomalies, cerebellar dysgenesis, and polysyndactyly. Developmental anomalies of the posterior fossa, including cerebellar hypoplasia and variants of the Dandy-Walker complex, are the most common central nervous system malformations reported in patients with this syndrome. We report hypothalamic hamartoma, supernumerary maxillary incisor, and precocious puberty in a boy with OFDS type VI. We propose that hypothalamic hamartoma is an occasional manifestation of OFDS type VI. © 1994 Wiley-Liss, Inc. 相似文献