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1.
Genet Med ; 20(11): 1468-1471, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29565416

RESUMEN

PURPOSE: Neonatal patients are particularly appropriate for utilization of diagnostic exome sequencing (DES), as many Mendelian diseases are known to present in this period of life but often with complex, heterogeneous features. We attempted to determine the diagnostic rates and features of neonatal patients undergoing DES. METHODS: The clinical histories and results of 66 neonatal patients undergoing DES were retrospectively reviewed. RESULTS: Clinical DES identified potentially relevant findings in 25 patients (37.9%). The majority of patients had structural anomalies such as birth defects, dysmorphic features, cardiac, craniofacial, and skeletal defects. The average time for clinical rapid testing was 8 days. CONCLUSION: Our observations demonstrate the utility of family-based exome sequencing in neonatal patients, including familial cosegregation analysis and comprehensive medical review.


Asunto(s)
Secuenciación del Exoma/métodos , Exoma/genética , Enfermedades Genéticas Congénitas/diagnóstico , Patología Molecular/métodos , Femenino , Enfermedades Genéticas Congénitas/genética , Humanos , Recién Nacido , Masculino , Mutación , Estudios Retrospectivos , Análisis de Secuencia de ADN
2.
Am J Med Genet A ; 170A(4): 967-77, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26692240

RESUMEN

We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458 bp (distal) and 53,160,114-53,713,154 bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication.


Asunto(s)
Duplicación Cromosómica , Cromosomas Humanos X , Estudios de Asociación Genética , Trastornos de los Cromosomas Sexuales/diagnóstico , Trastornos de los Cromosomas Sexuales/genética , Adolescente , Adulto , Anciano , Niño , Mapeo Cromosómico , Hibridación Genómica Comparativa , Facies , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Adulto Joven
3.
Am J Med Genet A ; 164A(1): 62-9, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24243649

RESUMEN

A syndrome associated with 19q13.11 microdeletions has been proposed based on seven previous cases that displayed developmental delay, intellectual disability, speech disturbances, pre- and post-natal growth retardation, microcephaly, ectodermal dysplasia, and genital malformations in males. A 324-kb critical region was previously identified as the smallest region of overlap (SRO) for this syndrome. To further characterize this microdeletion syndrome, we present five patients with deletions within 19q12q13.12 identified using a whole-genome oligonucleotide microarray. Patients 1 and 2 possess deletions overlapping the SRO, and Patients 3-5 have deletions proximal to the SRO. Patients 1 and 2 share significant phenotypic overlap with previously reported cases, providing further definition of the 19q13.11 microdeletion syndrome phenotype, including the first presentation of ectrodactyly in the syndrome. Patients 3-5, whose features include developmental delay, growth retardation, and feeding problems, support the presence of dosage-sensitive genes outside the SRO that may contribute to the abnormal phenotypes observed in this syndrome. Multiple genotype-phenotype correlations outside the SRO are explored, including further validation of the deletion of WTIP as a candidate for male hypospadias observed in this syndrome. We postulate that unique patient-specific deletions within 19q12q13.1 may explain the phenotypic variability observed in this emerging contiguous gene deletion syndrome.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 19 , Fenotipo , Anomalías Múltiples/genética , Adolescente , Niño , Preescolar , Hibridación Genómica Comparativa , Facies , Femenino , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Humanos , Lactante , Masculino , Síndrome
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