Dataset Information

Cytogenetic and molecular diagnosis of Fanconi anemia revealed two hidden phenotypes: Disorder of sex development and cerebro-oculo-facio-skeletal syndrome.

ABSTRACT:

Background

Several studies have shown a high rate of consanguinity and endogamy in North African populations. As a result, the frequency of autosomal recessive diseases is relatively high in the region with the co-occurrence of two or more diseases.

Methods

We report here on a consanguineous Libyan family whose child was initially diagnosed as presenting Fanconi anemia (FA) with uncommon skeletal deformities. The chromosome breakage test has been performed using mitomycin C (MMC) while molecular analysis was performed by a combined approach of linkage analysis and whole exome sequencing.

Results

Cytogenetic analyses showed that the karyotype of the female patient is 46,XY suggesting the diagnosis of a disorder of sex development (DSD). By looking at the genetic etiology of FA and DSD, we have identified p.[Arg798*];[Arg798*] mutation in FANCJ (OMIM #605882) gene responsible for FA and p.[Arg108*];[Arg1497Trp] in EFCAB6 (Gene #64800) gene responsible for DSD. In addition, we have incidentally discovered a novel mutation p.[Gly1372Arg];[Gly1372Arg] in the ERCC6 (CSB) (OMIM #609413) gene responsible for COFS that might explain the atypical severe skeletal deformities.

Conclusion

The co-occurrence of clinical and overlapping genetic heterogeneous entities should be taken into consideration for better molecular and genetic counseling.

SUBMITTER: Ben Haj Ali A

PROVIDER: S-EPMC6625148 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Cytogenetic and molecular diagnosis of Fanconi anemia revealed two hidden phenotypes: Disorder of sex development and cerebro-oculo-facio-skeletal syndrome.

Ben Haj Ali Abir A Amouri Ahlem A Sayeb Marwa M Makni Saloua S Hammami Wajih W Naouali Chokri C Dallali Hamza H Romdhane Lilia L Bashamboo Anu A McElreavey Kenneth K Abdelhak Sonia S Messaoud Olfa O

Molecular genetics & genomic medicine 20190523 7

<h4>Background</h4>Several studies have shown a high rate of consanguinity and endogamy in North African populations. As a result, the frequency of autosomal recessive diseases is relatively high in the region with the co-occurrence of two or more diseases.<h4>Methods</h4>We report here on a consanguineous Libyan family whose child was initially diagnosed as presenting Fanconi anemia (FA) with uncommon skeletal deformities. The chromosome breakage test has been performed using mitomycin C (MMC) ...[more]

PMID: 31124294

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Project description:Cerebro-oculo-facio-skeletal (COFS) syndrome is a recessively inherited rapidly progressive neurologic disorder leading to brain atrophy, with calcifications, cataracts, microcornea, optic atrophy, progressive joint contractures, and growth failure. Cockayne syndrome (CS) is a recessively inherited neurodegenerative disorder characterized by low to normal birth weight, growth failure, brain dysmyelination with calcium deposits, cutaneous photosensitivity, pigmentary retinopathy and/or cataracts, and sensorineural hearing loss. Cultured CS cells are hypersensitive to UV radiation, because of impaired nucleotide-excision repair (NER) of UV-induced damage in actively transcribed DNA, whereas global genome NER is unaffected. The abnormalities in CS are caused by mutated CSA or CSB genes. Another class of patients with CS symptoms have mutations in the XPB, XPD, or XPG genes, which result in UV hypersensitivity as well as defective global NER; such patients may concurrently have clinical features of another NER syndrome, xeroderma pigmentosum (XP). Clinically observed similarities between COFS syndrome and CS have been followed by discoveries of cases of COFS syndrome that are associated with mutations in the XPG and CSB genes. Here we report the first involvement of the XPD gene in a new case of UV-sensitive COFS syndrome, with heterozygous substitutions-a R616W null mutation (previously seen in patients in XP complementation group D) and a unique D681N mutation-demonstrating that a third gene can be involved in COFS syndrome. We propose that COFS syndrome be included within the already known spectrum of NER disorders: XP, CS, and trichothiodystrophy. We predict that future patients with COFS syndrome will be found to have mutations in the CSA or XPB genes, and we document successful use of DNA repair for prenatal diagnosis in triplet and singleton pregnancies at risk for COFS syndrome. This result strongly underlines the need for screening of patients with COFS syndrome, for either UV sensitivity or DNA-repair abnormalities.

Dataset Information

Cytogenetic and molecular diagnosis of Fanconi anemia revealed two hidden phenotypes: Disorder of sex development and cerebro-oculo-facio-skeletal syndrome.

Background

Methods

Results

Conclusion

Publications

Cytogenetic and molecular diagnosis of Fanconi anemia revealed two hidden phenotypes: Disorder of sex development and cerebro-oculo-facio-skeletal syndrome.

Similar Datasets

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