{"id":15839,"date":"2017-09-25T11:40:03","date_gmt":"2017-09-25T11:40:03","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=15839"},"modified":"2018-12-10T08:25:03","modified_gmt":"2018-12-10T08:25:03","slug":"role-of-arhgap29-gene-in-orofacial-clefting-a-systematic-review","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol10no3\/role-of-arhgap29-gene-in-orofacial-clefting-a-systematic-review\/","title":{"rendered":"Role of ARHGAP29 Gene in Orofacial Clefting : A Systematic Review"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Orofacial clefting has since time immemorial affected humans\u00a0 . It affects the\u00a0 individual in many ways ,which includes the\u00a0 phycological and\u00a0 physical aspects\u00a0 . The Incidence of orofacial clefts in India has been reported to be around 1:500.2<\/sup>\u00a0Orofacial clefts range\u00a0 from an isolated cleft around the face to a bilateral cleft lip and palate of the affected individual. The severe facial deformation associated with the clefting ,renders the affected individuals with\u00a0 a psychological set back. Some developing and underdeveloped\u00a0 countries suffer from a deficiency of sufficient health care for the patients with clefting. In countries like\u00a0 India where the cleft care does not reach the rural population , the severity of the psychological and physical effects can be felt\u00a0 .
\nThe search for eitiology of orofacial clefting has been a topic of contemporary\u00a0 research for quite sometime\u00a0 now. While the two forms of orofacial clefting, the syndromic and non syndromic clefting have been under research for a while now\u00a0 . The interest generated in\u00a0 non syndromic clefting has increased relatively more, as it involves an\u00a0 apparently healthy individual\u00a0 with orofacial clefting and without any other systemic condition.<\/p>\n

In\u00a0 1969 Carter proposed a model (MF\/T) 1<\/sup> multifactorial clefting\u00a0 inheritance, where he stated that non syndromic clefting was caused by the additive effects of minor abnormal genes and environmental factors.<\/p>\n

ARHGAP29 Gene<\/strong><\/p>\n

ARHGAP29\u00a0\u00a0gene is \u00a0found\u00a0 on the\u00a0 chromosome 1p22 that\u00a0 forms the\u00a0 Rho GTPase activating protein (GAP) 29,3<\/sup>\u00a0this protein\u00a0mediates the cyclical regulation of smaller GTP( binding) proteins such as RhoA.4 <\/sup><\/p>\n

Function<\/strong><\/p>\n

The gene ARHGAP29 is found in the developing face and may also act downstream of\u00a0IRF6\u00a0 gene in craniofacial development3<\/sup><\/p>\n

Structure<\/strong><\/p>\n

The Gene ARHGAP29 contains a total of four domains including a coiled-coil region, this is\u00a0 known to interact with the\u00a0 Rap2,6<\/sup>\u00a0the\u00a0 C1 domain, GTPase domain, the Rho, and a small C-terminal region that interacts with PTPL1.4<\/sup><\/p>\n

Clinical Significance<\/strong><\/p>\n

The 1p22 locus having the\u00a0 ARHGAP29 was long associated with nonsydromic\u00a0cleft lip\/palate clefting a\u00a0by genome wide association7<\/sup>\u00a0and meta-analysis.8<\/sup>\u00a0A follow-up study5 <\/sup>identified rare coding variants that\u00a0 included\u00a0 a nonsense and subsequently a\u00a0 frameshift variant in patients with nonsydromic\u00a0cleft lip\/palate. The gene\u00a0 ARHGAP29’s primary\u00a0 role in craniofacial development was found\u00a0 after an\u00a0 adjacent\u00a0ABCA4\u00a0gene lacked functional or expression data to support it as the main\u00a0 etiologic gene\u00a0 responsible for nonsydromic\u00a0cleft lip\/palate, \u00a0even though earlier the\u00a0 SNPs in the ABCA4 gene were associated with\u00a0 nonsyndromic\u00a0 cleft lip\/palate.<\/p>\n

To test the Null Hypothesis<\/strong><\/p>\n

The ARHGAP 29 gene\u00a0 mutation is responsible for\u00a0 orofacial clefting.<\/p>\n

Methodology <\/strong><\/p>\n

Three search bases , Pubmed , Science direct and Cochrane were searched using the key words.<\/p>\n

The Inclusion criteria used in the study was:<\/p>\n

A Direct association of the ARHGAP29 gene mutation to orofacial clefting
\nHuman subjects with Cleft<\/p>\n

Results<\/strong><\/p>\n

Pub med direct gave 22, Science direct 6 and Cochrane 0 articles.<\/p>\n

Further\u00a0 using the inclusion criteria, 3 articles were selected<\/p>\n

Discussion<\/strong><\/p>\n

The Role of ARHGap 29\u00a0 gene\u00a0 in Human orofacial clefting has\u00a0 been a topic of debate for sometime now, the\u00a0 present systematic review was designed to research\u00a0 if there were any human studies that implicated orofacial clefting to the ARHGAP29\u00a0 gene . In all the \u00a03 studies have implicated a direct relation to orofacial clefting . These studies have covered a broad research database spanning three major databases . Venkatesh Babu Gurramkonda et all9<\/sup> in a sample of 173 cases and 176 controls of nonsyndromic cleft lip and palate patients, could not find single nucleotide polymorphisms (SNP)\u00a0 located at chromosomal region 1p22, further the authors concluded that there was no link to south Indian non syndromic cleft lip & palate. Elizebeth J Leslie et all10<\/sup> in a study done on 182 individuals from the US and Phillipines affected with Nonsyndromic cleft lip & palate found that the gene\u00a0 ARHGAP29<\/em>\u00a0revealed eight potentially deleterious variants in cases including a frameshift and a nonsense variant. Deepak Chandrasekharan and Arvind ramanathan11<\/sup> reported a nonsense mutation in exon 1 of ARHGAP29 that caused substitution of lysine to stop codon at codon position 32 in a subject with nonsyndromic cleft lip with cleft palate among 60 patient samples. The reports of ARHGAP 29 gene in orofacial clefting is rare but has been reported from populations around the world.<\/p>\n

Conclusion<\/strong><\/p>\n

The ARHGAP 29 gene, \u00a0has been implicated in the formation of orofacial clefting. Several human studies have shown mutations in different populations.<\/p>\n

Conflict of Interest<\/strong><\/p>\n

The Authors would like to thank Bharath University for providing the facility for the study.<\/p>\n

There is no conflict of Interest.<\/p>\n

References<\/strong><\/p>\n

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