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2.
Indian J Ophthalmol ; 66(2): 334-336, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29380799

RESUMO

Here, we report a patient with oculodentodigital dysplasia (ODDD) caused by the c. 413G>A, p.Gly138Asp mutation in the gap junction protein alpha-1 gene. The patient suffered from characteristic dysmorphic features of ODDD. Ophthalmological investigation disclosed microcornea and a shallow anterior chamber, as expected. Surprisingly, the patient had a normal axial length and moderate myopia on both eyes. To the best of our knowledge, this is the first report on ODDD associated with relative anterior microphthalmos and myopia.


Assuntos
Anormalidades Múltiplas , Conexina 43/genética , Anormalidades Craniofaciais/diagnóstico , DNA/genética , Anormalidades do Olho/diagnóstico , Deformidades Congênitas do Pé/diagnóstico , Microftalmia/diagnóstico , Sindactilia/diagnóstico , Anormalidades Dentárias/diagnóstico , Adulto , Conexina 43/metabolismo , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/metabolismo , Análise Mutacional de DNA , Anormalidades do Olho/genética , Anormalidades do Olho/metabolismo , Deformidades Congênitas do Pé/genética , Deformidades Congênitas do Pé/metabolismo , Humanos , Masculino , Microftalmia/genética , Microftalmia/metabolismo , Sindactilia/genética , Sindactilia/metabolismo , Tomografia de Coerência Óptica , Anormalidades Dentárias/genética , Anormalidades Dentárias/metabolismo
4.
Ann Lab Med ; 38(1): 54-58, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29071820

RESUMO

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%). Among the LQTS-related genes, we detected a previously reported pathogenic variant, CACNA1C c.1552C>T, responsible for cardiac-only Timothy syndrome. Among the genes related to other cardiac diseases, a likely pathogenic variant, RYR2 c.11995A>G, was identified in a patient with catecholaminergic polymorphic ventricular tachycardia. Another patient who developed dilated cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy. Comprehensive screening of genetic variants using multigene panel sequencing enables detection of genetic variants with a possible involvement in QTc interval prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.


Assuntos
Canal de Potássio ERG1/genética , Canal de Potássio KCNQ1/genética , Síndrome do QT Longo/diagnóstico , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Adolescente , Adulto , Transtorno Autístico/diagnóstico , Transtorno Autístico/genética , Canais de Cálcio Tipo L/genética , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Criança , Pré-Escolar , Eletrocardiografia , Testes Genéticos , Variação Genética , Humanos , Lactente , Síndrome do QT Longo/genética , Polimorfismo de Nucleotídeo Único , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Sindactilia/diagnóstico , Sindactilia/genética , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/genética , Fatores de Transcrição/genética , Adulto Jovem
5.
J Hand Surg Am ; 43(2): 186.e1-186.e16, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29033291

RESUMO

PURPOSE: Poland syndrome was first described as a deficiency of the pectoral muscle with ipsilateral symbrachydactyly. Currently, numerous case reports describe variations of Poland syndrome in which pectoral muscle deficiency is often used as the only defining criterion. However, more syndromes can present with pectoral muscle deficiency. The aim of this review is to illustrate the diversity of the phenotypic spectrum of Poland syndrome and to create more awareness for alternative diagnoses in pectoral muscle deficiency. METHODS: A systematic literature search was performed. Articles containing phenotypical descriptions of Poland syndrome were included. Data extraction included number of patients, sex, familial occurrence, and the definition of Poland syndrome used. In addition, hand deformities, thoracic deformities, and other deformities in each patient were recorded. Alternative syndrome diagnoses were identified in patients with a combination of hand, thorax, and other deformities. RESULTS: One hundred-and-thirty-six articles were included, describing 627 patients. Ten different definitions of Poland syndrome were utilized. In 58% of the cases, an upper extremity deformity was found and 43% of the cases had an associated deformity. Classic Poland syndrome was seen in 29%. Fifty-seven percent of the patients with a pectoral malformation, a hand malformation, and another deformity had at least 1feature that matched an alternative syndrome. CONCLUSIONS: Pectoral muscle hypoplasia is not distinctive for Poland syndrome alone but is also present in syndromes with other associated anomalies with a recognized genetic cause. Therefore, in patients with an atypical phenotype, we recommend considering other diagnoses and/or syndromes before diagnosing a patient with Poland syndrome. This can prevent diagnostic and prognostic errors. CLINICAL RELEVANCE: Differentiating Poland syndrome from the alternative diagnoses has serious consequences for the patient and their family in terms of inheritance and possible related anomalies.


Assuntos
Síndrome de Poland/diagnóstico , Anormalidades Múltiplas/diagnóstico , Diagnóstico Diferencial , Humanos , Músculos Peitorais/anormalidades , Fenótipo , Sindactilia/diagnóstico , Deformidades Congênitas das Extremidades Superiores/diagnóstico
6.
Am J Med Genet A ; 173(12): 3226-3230, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29088509

RESUMO

The STAR syndrome is a rare X-linked dominant developmental disorder caused by point mutations in the single FAM58A gene or deletions involving FAM58A and its flanking genes. The STAR phenotype is characterized by a rather homogeneous constellation of facial dysmorphisms and malformations summarized by its acronym, Syndactyly, Telecanthus, Anogenital, and Renal malformations. Here we describe a female patient with STAR syndrome and a 130 kb deletion at Xq28, including the FAM58A gene. She presented with cleft lip palate, omphalocele, and cerebral malformations not previously considered part of the phenotypic spectrum of this syndrome. She died at 6 weeks from respiratory failure.


Assuntos
Canal Anal/anormalidades , Fissura Palatina/genética , Ciclinas/genética , Hipertelorismo/genética , Rim/anormalidades , Sindactilia/genética , Dedos do Pé/anormalidades , Anormalidades Urogenitais/genética , Canal Anal/patologia , Bandeamento Cromossômico , Fissura Palatina/diagnóstico , Fissura Palatina/patologia , Evolução Fatal , Feminino , Humanos , Hipertelorismo/diagnóstico , Hipertelorismo/patologia , Recém-Nascido , Cariotipagem , Rim/patologia , Mutação Puntual , Sindactilia/diagnóstico , Sindactilia/patologia , Dedos do Pé/patologia , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/patologia
7.
BMJ Case Rep ; 20172017 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-29103005

RESUMO

The impact of in-utero isotretinoin exposure has been widely reported, with many affected pregnancies failing to reach term.1 2 Due to the low numbers of in-utero isotretinoin exposed pregnancies, the interactions between this drug and rare genetic defects such as microduplication 1q21.1 are unclear, particularly how they might manifest phenotypically. We present this case of in-utero isotretinoin exposure occurring in a child with microduplication 1q21.1. The child was born with congenital abnormalities which did not fit into a single syndrome. Regrettably in-utero exposure to isotretinoin continues to occur. We hope this case will trigger further discussion on the dangers of dispensing Isotretinoin without ensuring stringent pregnancy testing and its potential interaction with genetic abnormalities, in particular with microduplication 1q21.1.


Assuntos
Anormalidades Induzidas por Medicamentos/genética , Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Isotretinoína/toxicidade , Sindactilia/diagnóstico , Teratogênios/toxicidade , Anormalidades Induzidas por Medicamentos/diagnóstico , Anormalidades Induzidas por Medicamentos/diagnóstico por imagem , Fenda Labial/induzido quimicamente , Fenda Labial/diagnóstico por imagem , Fissura Palatina/induzido quimicamente , Fissura Palatina/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Dedos/anormalidades , Humanos , Lactente , Imagem por Ressonância Magnética , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Sindactilia/induzido quimicamente , Sindactilia/diagnóstico por imagem , Dedos do Pé/anormalidades
8.
Am J Med Genet A ; 173(11): 3114-3117, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28940926

RESUMO

CHAND syndrome is an autosomal recessive disorder characterized by curly hair, ankyloblepharon, and nail dysplasia. Only few patients were reported to date. A homozygous RIPK4 mutation was recently identified by homozygosity mapping and whole exome sequencing in three patients from an expanded consanguineous kindred with a clinical diagnosis of CHAND syndrome. RIPK4 was previously known to be implicated in Bartsocas-Papas syndrome, the autosomal recessive form of popliteal pterygium syndrome. We report here two cases of RIPK4 homozygous mutations in a fetus with severe Bartsocas-Papas syndrome and a patient with CHAND syndrome. The patient with CHAND syndrome harbored the same mutation as the one identified in the family previously reported. We thus confirm the implication of RIPK4 gene in CHAND syndrome in addition to Bartsocas-Papas syndrome and discuss genotype/phenotype correlations.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Anormalidades do Olho/genética , Doenças Palpebrais/genética , Doenças do Cabelo/genética , Joelho/anormalidades , Transtornos do Desenvolvimento da Linguagem/genética , Unhas Malformadas/genética , Proteínas Serina-Treonina Quinases/genética , Sindactilia/genética , Pré-Escolar , Fenda Labial/diagnóstico , Fenda Labial/fisiopatologia , Fissura Palatina/diagnóstico , Fissura Palatina/fisiopatologia , Consanguinidade , Exoma/genética , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/fisiopatologia , Doenças Palpebrais/diagnóstico , Doenças Palpebrais/fisiopatologia , Feminino , Feto , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/fisiopatologia , Homozigoto , Humanos , Recém-Nascido , Joelho/fisiopatologia , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Masculino , Mutação , Unhas Malformadas/diagnóstico , Unhas Malformadas/fisiopatologia , Sindactilia/diagnóstico , Sindactilia/fisiopatologia
9.
Taiwan J Obstet Gynecol ; 56(3): 398-401, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28600059

RESUMO

OBJECTIVE: We present prenatal diagnosis and molecular genetic characterization of a de novo interstitial deletion of 2q (2q31.1-q32.1) and discuss the genotype-phenotype correlation. CASE REPORT: A 34-year-old, primigravid woman was referred to the hospital at 20 weeks of gestation for genetic counseling because of a prenatally detected de novo interstitial deletion of chromosome 2q (2q31.1-q32.1). She underwent amniocentesis at 17 weeks of gestation because of advanced maternal age and an increased first-trimester nuchal translucency (NT) thickness of 3.6 mm. Amniocentesis revealed a karyotype of 46,XY. However, array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniotic fluid and amniocytes revealed a 13.29-Mb deletion at chromosome 2q31.3-q32.1. The parents did not have such a deletion. Prenatal ultrasound findings were unremarkable. After counseling of the genotype-phenotype correlation of such a chromosome aberration with congenital malformations, the parents elected to terminate the pregnancy. The fetus postnataly manifested hypertelorism and syndactyly of the second and third toes of bilateral feet. Cytogenetic analysis of the umbilical cord revealed a karyotype of 46,XY,del(2)(q31q32). aCGH analysis on the DNA extracted from the cord blood confirmed a 13.35-Mb deletion of 2q31.1-q32.1 encompassing HOXD13, ZNF385B, ITGA4, CERKL, PDE1A, FRZB and ZNF804A. Polymorphic DNA marker analysis revealed a paternal origin of the deletion. CONCLUSION: Fetuses with an interstitial deletion of 2q31.1-q32.1 may be associated with increased first-trimester NT. Haploinsufficiency of HOXD13 is associated with syndactyly. Genomic microarray is useful in detecting subtle chromosomal abnormalities in fetuses with increased NT and normal karyotype.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 2 , Hipertelorismo/genética , Medição da Translucência Nucal , Sindactilia/genética , Aborto Eugênico , Adulto , Hibridização Genômica Comparativa , Feminino , Marcadores Genéticos , Proteínas de Homeodomínio , Humanos , Hipertelorismo/diagnóstico , Fatores de Transcrição Kruppel-Like , Gravidez , Primeiro Trimestre da Gravidez , Sindactilia/diagnóstico , Fatores de Transcrição
10.
Eur J Med Genet ; 60(8): 421-425, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28559208

RESUMO

Cenani-Lenz syndactyly syndrome (CLSS; MIM-212780) is a rare autosomal recessive limb malformation characterized by complete osseous fusion of all fingers and toes, disorganization of phalangeal elements and severe shortening of the radius and ulna. It is occasionally associated with renal hypoplasia, oro-facial defects, scoliosis of the thoracic spine, hearing loss, and genital anomalies. Here we describe a consanguineous Pakistani kindred with a severe form of CLSS characterized by complete syndactyly and disorganization of fingers, oligo-syndactyly of toes, shortening of limbs, frontal bossing, and hypoplasia/agenesis of left kidney. The affected individuals were additionally presented with short stature, cleft-lip and hypoplastic shoulder joint with restricted upper limb movement. A novel splice variant in LRP4 (c.316+1G > A) segregated with the phenotype in a five generations family. The mutation is predicted to add 29 non-native amino acids with a premature termination, resulting in approximately 90% length reduction of the wild-type transcript. These findings not only further expand the phenotypic variability of CLSS but also indicate that early truncated and loss-of-function mutations in LRP4 lead to a more severe CLSS phenotype.


Assuntos
Proteínas Relacionadas a Receptor de LDL/genética , Mutação , Processamento de RNA , Sindactilia/genética , Criança , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Sindactilia/diagnóstico
11.
Mol Med Rep ; 16(1): 473-477, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28498426

RESUMO

Syndactyly is one of the most common hereditary limb malformations, and is characterized by the fusion of specific fingers and/or toes. Syndactyly type I­c is associated with bilateral cutaneous or bony webbing of the third and fourth fingers and occasionally of the third to fifth fingers, with normal feet. The aim of the present study was to identify the genetic basis of syndactyly type I­c in four generations of a Chinese Han family by exome sequencing. Exome sequencing was conducted in the proband of the family, followed by direct sequencing of other family members of the same ancestry, as well as 100 ethnically­matched, unrelated normal controls. A missense mutation, c.917G>A (p.R306Q), was identified in the homeobox D13 gene (HOXD13). Sanger sequencing verified the presence of this mutation in all of the affected family members. By contrast, this mutation was absent in the unaffected family members and the 100 ethnically­matched normal controls. The results suggest that the c.917G>A (p.R306Q) mutation in the HOXD13 gene, may be responsible for syndactyly type I­c in this family. Exome sequencing may therefore be a powerful tool for identifying mutations associated with syndactyly, which is a disorder with high genetic and clinical heterogeneity. The results provide novel insights into the etiology and diagnosis of syndactyly, and may influence genetic counseling and the clinical management of the disease.


Assuntos
Proteínas de Homeodomínio/genética , Mutação de Sentido Incorreto , Sindactilia/diagnóstico , Sindactilia/genética , Fatores de Transcrição/genética , Sequenciamento Completo do Exoma , Adolescente , Adulto , Sequência de Aminoácidos , Criança , China , Análise Mutacional de DNA , Feminino , Heterozigoto , Proteínas de Homeodomínio/química , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Fatores de Transcrição/química , Adulto Jovem
12.
J Craniofac Surg ; 28(3): e250-e251, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28468208

RESUMO

Popliteal pterygium syndrome is a condition characterized by skin webs on the popliteal fossa, which may impair mobility unless surgically repaired. Affected individuals may also have syndactyly on the fingers and/or toes. Most people with this disorder present cleft lip and cleft palate and they can have syngnathia, that is a congenital adhesion between maxilla and mandible by fibrous bands, which affects the opening of the mouth. The case that we report is about a 2-month-old male, who presented skin webs bilaterally on the popliteal fossa, syndactyly between the IV and the V toe of the right foot and between the III and the IV toe of the left foot, and genital malformations. He was born with complete bilateral cleft lip and complete cleft palate on the left side and incomplete cleft palate on the right side and syngnathia with 4 fibrous bands between the mandibular arch and the maxilla arch on the right side, which affected the opening of the mouth. The case of our patient is very interesting because there have been few reported patients affected by popliteal pterygium syndrome with syngnathia.


Assuntos
Anormalidades Múltiplas/diagnóstico , Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Anormalidades do Olho/diagnóstico , Dedos/anormalidades , Articulação do Joelho/anormalidades , Deformidades Congênitas das Extremidades Inferiores/diagnóstico , Mandíbula/anormalidades , Maxila/anormalidades , Sindactilia/diagnóstico , Anormalidades Urogenitais/diagnóstico , Humanos , Lactente , Masculino
13.
Ortop Traumatol Rehabil ; 19(1): 75-78, 2017 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-28436373

RESUMO

FATCO syndrome consists of fibular hemimelia, tibial campomelia and oligosyndactyly. FATCO syndrome can also be associated with other congenital anomalies; therefore, every case needs thorough evaluation so as to make the management of the patient easier. A few cases of this syndrome have been described in literature but only two cases have been reported in India so far. We present a 3-year-old male child born of a non-con-sanguinous marriage with FATCO syndrome and ipilateral talar aplasia without any other congenital anomalies.


Assuntos
Displasia Campomélica/diagnóstico , Displasia Campomélica/terapia , Fíbula/anormalidades , Dedos/anormalidades , Deformidades Congênitas do Pé/diagnóstico , Deformidades Congênitas do Pé/terapia , Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/terapia , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/terapia , Doenças Raras/diagnóstico , Doenças Raras/terapia , Sindactilia/diagnóstico , Sindactilia/terapia , Tíbia/anormalidades , Dedos do Pé/anormalidades , Displasia Campomélica/fisiopatologia , Pré-Escolar , Fíbula/fisiopatologia , Dedos/fisiopatologia , Deformidades Congênitas do Pé/fisiopatologia , Deformidades Congênitas da Mão/fisiopatologia , Humanos , Índia , Deformidades Congênitas dos Membros/fisiopatologia , Masculino , Sindactilia/fisiopatologia , Tíbia/fisiopatologia , Dedos do Pé/fisiopatologia , Resultado do Tratamento
14.
Am J Med Genet A ; 173(3): 784-789, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28211989

RESUMO

Timothy syndrome 1 (TS1) is a rare genetic disorder characterized by multisystem abnormalities including QT prolongation, congenital heart defects, facial dysmorphism, episodic hypoglycemia, and neurological symptoms. A morphological hallmark of TS1 is syndactyly, present in all cases. TS1 is caused by the canonical p.Gly406Arg mutation in the alternatively spliced exon 8A in the CACNA1C gene, encoding for the main cardiac L-type calcium channel. A variant case of TS1 is reported. The proband had intermittent fetal bradycardia with heart rate of 72 bpm. On the first day of life bradycardia due to 2:1 atrioventricular (AV) block and marked QTc prolongation of 600 ms was noted. On medical therapy with propranolol and mexiletine 1:1 AV conduction returned with QTc prolongation of 470-580 ms. The patient lacked other extracardiac manifestations, most importantly syndactyly, neurological complications or autism. On genetic analysis, the canonical TS1 causing mutation, p.Gly406Arg in exon 8A of the CACNA1C gene was detected. The CACNA1C p.Gly406Arg variant was not present in the parents, but was detected in different DNA samples of the index patient. Our case highlight further phenotypic variability in TS. Most importantly, it underlines that the lack of syndactyly does not exclude the presence of a TS1 genotype. © 2017 Wiley Periodicals, Inc.


Assuntos
Transtorno Autístico/diagnóstico , Transtorno Autístico/genética , Canais de Cálcio Tipo L/genética , Estudos de Associação Genética , Genótipo , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/genética , Fenótipo , Sindactilia/diagnóstico , Sindactilia/genética , Alelos , Substituição de Aminoácidos , Biomarcadores , Análise Mutacional de DNA , Ecocardiografia , Eletrocardiografia , Éxons , Humanos , Recém-Nascido , Masculino , Mutação
16.
J Am Dent Assoc ; 148(3): 157-163, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28043400

RESUMO

BACKGROUND AND OVERVIEW: Lacrimo-auriculo-dento-digital (LADD) syndrome is an autosomal dominant disorder with variable lacrimal and salivary gland hypoplasia and aplasia, auricular anomalies and hearing loss, dental defects and caries, and digital anomalies. CASE DESCRIPTION: The authors present the cases of 2 unrelated children with enamel defects and history of dry mouth leading to recurrent dental caries. The referring diagnoses were Sjögren disease and hypohidrotic ectodermal dysplasia, respectively. The geneticist suspected LADD syndrome, which was confirmed by means of molecular studies showing mutations of 2 genes: fibroblast growth factor receptor 2 and fibroblast growth factor 10, respectively. Similarly affected relatives indicated an autosomal dominant inheritance. These relatives needed multiple dental rehabilitations during childhood and dentures in adulthood. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Dry mouth, multiple caries, enamel defects, and abnormal tooth morphology were the reasons for seeking care from dentists. However, clinical evaluation and diagnostic imaging studies helped identify anomalies of the lacrimal and salivary glands, ears, and digits, indicating involvement of different areas of the body, compatible with LADD syndrome. Accordingly, dentists should consider genetic disorders in patients with multiple anomalies. For instance, oculodentodigital syndrome, oral-facial-digital syndrome, and LADD syndrome (among others) may have dental issues as the major clinical manifestation. Accurate identification of a particular syndrome is now commonplace with the use of genetic testing. When a patient has multiple anomalies suggestive of a syndromic condition, appropriate genetic testing can help verify the clinical diagnosis. Keeping genetics in mind helps earlier identification of other affected family members with diagnostic genetic testing and appropriate treatment; the economic advantage is to shorten the diagnostic odyssey and possibly preserve dentition.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Assistência Odontológica para Crianças , Assistência Odontológica para Doentes Crônicos , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/genética , Sindactilia/diagnóstico , Sindactilia/genética , Anormalidades Dentárias/diagnóstico , Anormalidades Dentárias/genética , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Mutação , Linhagem
17.
Congenit Anom (Kyoto) ; 57(1): 4-7, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27254532

RESUMO

Synpolydactyly (SPD) is an autosomal dominant limb malformation with a distinctive combination of syndactyly and polydactyly. SPD is clinically heterogeneous and could be genetically classified into three types. The clinical phenotype of SPD is complicated by its variable expressivity. In the present study, whole exome sequencing (WES) was used to identify the affected gene(s) in a Chinese family with atypical SPD phenotype. Our results showed that a novel heterogenous nonsense mutation (c.556C > T, p.R186X) in HOXD13 was associated with this SPD case. Due to variable expressivity, the diagnosis of a clinical heterogenous disease such as SPD is usually difficult. Our results also suggested that WES is an efficient tool to assist with these diagnoses.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Códon sem Sentido , Exoma , Proteínas de Homeodomínio/genética , Sindactilia/diagnóstico , Sindactilia/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , China , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Linhagem , Fenótipo
19.
Am J Med Genet A ; 173(2): 531-536, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27868338

RESUMO

Autosomal dominant genetic diseases can occur de novo and in the form of somatic mosaicism, which can give rise to a less severe phenotype, and make diagnosis more difficult given the sensitivity limits of the methods used. We report the case of female child with a history of surgery for syndactyly of the hands and feet, who was admitted at 6 years of age to a pediatric intensive care unit following cardiac arrest. The electrocardiogram (ECG) showed a long QT interval that on occasions reached 500 ms. Despite the absence of facial dysmorphism and the presence of normal psychomotor development, a diagnosis of Timothy syndrome was made given the association of syndactyly and the ECG features. Sanger sequencing of the CACNA1C gene, followed by sequencing of the genes KCNQ1, KCNH2, KCNE1, KCNE2, were negative. The subsequent analysis of a panel of genes responsible for hereditary cardiac rhythm disorders using Haloplex technology revealed a recurrent mosaic p.Gly406Arg missense mutation of the CACNA1C gene in 18% of the cells. This mosaicism can explain the negative Sanger analysis and the less complete phenotype in this patient. Given the other cases in the literature, mosaic mutations in Timothy syndrome appear more common than previously thought. This case demonstrates the importance of using next-generation sequencing to identify mosaic mutations when the clinical picture supports a specific mutation that is not identified using conventional testing. © 2016 Wiley Periodicals, Inc.


Assuntos
Transtorno Autístico/diagnóstico , Transtorno Autístico/genética , Canais de Cálcio Tipo L/genética , Estudos de Associação Genética , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/genética , Mosaicismo , Mutação , Fenótipo , Sindactilia/diagnóstico , Sindactilia/genética , Alelos , Substituição de Aminoácidos , Criança , Códon , Análise Mutacional de DNA , Eletrocardiografia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
20.
J Nepal Health Res Counc ; 14(33): 135-139, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27885298

RESUMO

Klippel-Trenaunaysyndrome(KTS) is a rare congenital condition usually presenting with port wine stains, excessive growth of bones and soft tissue and varicose veins which most commonly occurs in the legs, but it also may affect the arms, face, head, or internal organs. We report a case of term male neonate with clinical findings of Port-wine stain, multiple cystic swellings with ultrasonographic findings suggestive of vascular malformations and limb abnormalities in the form ofsoft tissue hypertrophy of right upper limb, polydactyly of right hand and syndactyly of left hand consistent withKlippel-Trenaunay syndrome.


Assuntos
Síndrome de Klippel-Trenaunay-Weber/diagnóstico , Humanos , Recém-Nascido , Síndrome de Klippel-Trenaunay-Weber/patologia , Masculino , Polidactilia/complicações , Polidactilia/diagnóstico , Mancha Vinho do Porto/complicações , Mancha Vinho do Porto/diagnóstico , Sindactilia/complicações , Sindactilia/diagnóstico
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