ABSTRACT
Terminal 7q duplication and terminal 13q deletion are two conditions with variable phenotypes including microcephaly, thumb a-/hypoplasia, cortical dysplasia, microphtalmia, intellectual disability and dysmorphic features. We describe a boy born to a mother with a reciprocal t (7;13) who combines both a terminal 7q33-qter duplication and terminal 13q33-qter deletion through the inheritance of a derivative chromosome 13 (der (13)). The patient presented with developmental delay, facial and non-facial dysmorphic features, hypertonia, genital abnormality and skeletal malformation but no thumb a-/hypoplasia or microphtalmia. Knowing the exact breakpoints of his chromosomal aberrations using high resolution array CGH (aCGH) and comparison of his phenotypes with those of 24 and 59 previously published cases of 7q duplication and 13q deletion, respectively, allow us to further narrow the size of the proposed critical regions for microcephaly, thumb a-/hypoplasia and hypo/hypertonia on chromosome 13.
Subject(s)
Abnormalities, Multiple/diagnosis , Chromosome Disorders/diagnosis , Sexual Development/genetics , Trisomy/diagnosis , Abnormalities, Multiple/genetics , Child, Preschool , Chromosome Deletion , Chromosome Disorders/genetics , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 7/genetics , Comparative Genomic Hybridization , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Male , Oligonucleotide Array Sequence Analysis , Phenotype , Trisomy/geneticsABSTRACT
Mitochondria have essential role in cellular energy metabolism and defects in their function lead to many metabolic diseases. Mitochondrial DNA (mtDNA) mutations have been associated with number diseases such as nonsyndromic and aminoglycoside-induced hearing loss. Mutational screening of entire 12SrRNA and tRNA (ser (UCN)) genes in 107 unrelated Iranian patients with amino glycoside-induced and nonsyndromic bilateral hearing loss by direct sequencing analysis method were performed. Twenty different homoplasmic sequence variants were identified; including fifteen common polymorphisms, two putatively pathogenic variants: m.921T>C and m.1005T>C, one 12SrRNA sequence variant m.739C>T and two nucleotides substitution; m.1245T>C and m.1545T>C. Deafness-associated mutation, m.1555A>G, was not found. In our patients we found the mutation 1005 was associated with R haplogroup. These finding show that m.1555A>G mutation is not important in our population. Nucleotide change, m.739C>T, previously reported with very low frequency. We suggested the variation of two nucleotides 1245 and 1545 that localized at conserved site of 12SrRNA may be new candidate for amino glycoside-induced and nonsyndromic hearing impairment associated mutations. However, aminoglycoside exposure is a risk factor for clinical phenotype appearance of these mutations.
Subject(s)
Aminoglycosides/adverse effects , Genes, Mitochondrial , Hearing Loss/chemically induced , Hearing Loss/genetics , Mutation , RNA, Ribosomal/genetics , Adolescent , Child , Child, Preschool , DNA Mutational Analysis , Female , Haplotypes , Humans , Male , Young AdultABSTRACT
We present a patient with non-syndromic and sensorineural hearing impairment with a novel mitochondrial DNA transition. A 7-year-old boy showed progressive deafness. He gradually lost his hearing ability and his hearing function did not improve with hearing aids. Laboratory data revealed normal blood lactate and pyruvate levels. Genetic analyses for mitochondrial DNA and GJB2 and GJB6 genes were performed. Mitochondrial genes analysis revealed a novel heteroplasmic nucleotide substitution, m.628C>T, in the phenylalanine transfer RNA gene. This case study reveals m.628C>T transition as a novel mitochondrial nucleotide change which may be important in mitochondrial deafness.
