A mutation in <it>KIF7</it> is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance
<p><b>Abstract</b></p> <p><b>Background</b></p> <p>We previously reported the existence of a unique autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance mapping to chromosome 15q...
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| Format: | Article |
| Language: | English |
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BMC
2012-05-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | http://www.ojrd.com/content/7/1/27 |
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| author | Ali Bassam R Silhavy Jennifer L Akawi Nadia A Gleeson Joseph G Al-Gazali Lihadh |
| author_facet | Ali Bassam R Silhavy Jennifer L Akawi Nadia A Gleeson Joseph G Al-Gazali Lihadh |
| author_sort | Ali Bassam R |
| collection | DOAJ |
| description | <p><b>Abstract</b></p> <p><b>Background</b></p> <p>We previously reported the existence of a unique autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance mapping to chromosome 15q26.</p> <p><b>Methods</b></p> <p>In this manuscript, we have used whole exome sequencing on two affected members of a consanguineous family with this condition and carried out detailed bioinformatics analysis to elucidate the causative mutation.</p> <p><b>Results</b></p> <p>Our analysis resulted in the identification of a homozygous p.N1060S missense mutation in a highly conserved residue in KIF7, a regulator of Hedgehog signaling that has been recently found to be causing Joubert syndrome, fetal hydrolethalus and acrocallosal syndromes. The phenotype in our patients partially overlaps with the phenotypes associated with those syndromes but they also exhibit some distinctive features including multiple epiphyseal dysplasia.</p> <p><b>Conclusions</b></p> <p>We report the first missense homozygous disease-causing mutation in <it>KIF7</it> and expand the clinical spectrum associated with mutations in this gene to include multiple epiphyseal dysplasia. The missense nature of the mutation might account for the unique presentation in our patients.</p> |
| first_indexed | 2024-12-14T01:51:07Z |
| format | Article |
| id | doaj.art-84abf2a7b5244749939e3b3fd8cacf9b |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-14T01:51:07Z |
| publishDate | 2012-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-84abf2a7b5244749939e3b3fd8cacf9b2022-12-21T23:21:23ZengBMCOrphanet Journal of Rare Diseases1750-11722012-05-01712710.1186/1750-1172-7-27A mutation in <it>KIF7</it> is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearanceAli Bassam RSilhavy Jennifer LAkawi Nadia AGleeson Joseph GAl-Gazali Lihadh<p><b>Abstract</b></p> <p><b>Background</b></p> <p>We previously reported the existence of a unique autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance mapping to chromosome 15q26.</p> <p><b>Methods</b></p> <p>In this manuscript, we have used whole exome sequencing on two affected members of a consanguineous family with this condition and carried out detailed bioinformatics analysis to elucidate the causative mutation.</p> <p><b>Results</b></p> <p>Our analysis resulted in the identification of a homozygous p.N1060S missense mutation in a highly conserved residue in KIF7, a regulator of Hedgehog signaling that has been recently found to be causing Joubert syndrome, fetal hydrolethalus and acrocallosal syndromes. The phenotype in our patients partially overlaps with the phenotypes associated with those syndromes but they also exhibit some distinctive features including multiple epiphyseal dysplasia.</p> <p><b>Conclusions</b></p> <p>We report the first missense homozygous disease-causing mutation in <it>KIF7</it> and expand the clinical spectrum associated with mutations in this gene to include multiple epiphyseal dysplasia. The missense nature of the mutation might account for the unique presentation in our patients.</p>http://www.ojrd.com/content/7/1/27KIF7AcrocallosalJoubertSonic hedgehogDysmorphismMultiple epiphyseal dysplasiaFetal hydrolethalus |
| spellingShingle | Ali Bassam R Silhavy Jennifer L Akawi Nadia A Gleeson Joseph G Al-Gazali Lihadh A mutation in <it>KIF7</it> is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance Orphanet Journal of Rare Diseases KIF7 Acrocallosal Joubert Sonic hedgehog Dysmorphism Multiple epiphyseal dysplasia Fetal hydrolethalus |
| title | A mutation in <it>KIF7</it> is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance |
| title_full | A mutation in <it>KIF7</it> is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance |
| title_fullStr | A mutation in <it>KIF7</it> is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance |
| title_full_unstemmed | A mutation in <it>KIF7</it> is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance |
| title_short | A mutation in <it>KIF7</it> is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance |
| title_sort | mutation in it kif7 it is responsible for the autosomal recessive syndrome of macrocephaly multiple epiphyseal dysplasia and distinctive facial appearance |
| topic | KIF7 Acrocallosal Joubert Sonic hedgehog Dysmorphism Multiple epiphyseal dysplasia Fetal hydrolethalus |
| url | http://www.ojrd.com/content/7/1/27 |
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