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Emory Genetics Aarskog-Scott syndrome (FGD1 Mutation)
Test CodeTG
CPT Codes
81479 (x1)
Preferred Specimen
Whole Blood
Other Acceptable Specimens
Saliva Oragene Saliva Collection kit (available through EGL) used according to manufacturer instructions. Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
Instructions
Please submit copies of diagnostic biochemical test results along with the sample, if appropriate. Contact the laboratory if further information is needed. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of Emory Genetics Laboratory, please submit a copy of the sequencing report with the test requisition
Transport Container
"In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
"
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
"
Transport Temperature
"Whole Blood In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overni
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overni
Specimen Stability
Room Temperature
Methodology
PCR amplification of 18 exons contained in the FGD1 gene is performed on the patient's genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions using automated fluorescence dideoxy sequencing methods. The patient's gene sequences are then compared to a normal reference sequence. Sequence variations are classified as mutations, benign variants unrelated to disease, or variations of unknown clinical significance. Variants of unknown clinical significance may require further studies of the patient and/or family members. This assay does not interrogate the promoter region, deep intronic regions or other regulatory elements, and does not detect large deletions.
Report Available
4 weeks
Clinical Significance
"Aarskog-Scott syndrome (faciogenital dysplasia) is an X-linked disorder characterized by facial, skeletal, and genital anomalies, although expressivity is highly variable. The main features are:
• Short stature
• Ocular hypertelorism
• Anteverted nostrils
• Broad upper lip
• Brachydactyly
• ""Shawl scrotum"" in males.
Other symptoms can include ligamentous laxity manifested by hyperextensibility of the fingers, genu recurvatum, and flat feet. Congenital heart defects have been demonstrated in some patients. A spectrum of behavioral disorders and intellectual disability may also be part of the Aarskog-Scott syndrome phenotype. Female carriers may show some minor manifestations of the disorder, especially in the face and hands.
Mutations in the FGD1 gene (Xp11.21) have been associated with both Aarskog-Scott syndrome and non-syndromic X-linked intellectual disability. One study identified FGD1 mutations in 8 of 46 male patients with a clinical diagnosis of Aarskog-Scott syndrome, including 4 deletions, 1 insertion, and 3 missense mutations. The mutations were scattered over the entire coding sequence, and there were no apparent genotype/phenotype correlations. No global differences in clinical findings were found between probands with or without mutations, but those with mutations presented with a fuller clinical spectrum of the phenotype. Mutations have also been found in a male with attention deficit-hyperactivity disorder (ADHD) and low intelligence quotient with dysmorphic features reminiscent of Aarskog-Scott syndrome, and in three brothers with non-syndromal X-linked mental retardation who lacked distinct craniofacial, skeletal, or genital findings, suggestive of Aarskog-Scott syndrome.
For patients with suspected Aarskog-Scott syndrome, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.
"
• Short stature
• Ocular hypertelorism
• Anteverted nostrils
• Broad upper lip
• Brachydactyly
• ""Shawl scrotum"" in males.
Other symptoms can include ligamentous laxity manifested by hyperextensibility of the fingers, genu recurvatum, and flat feet. Congenital heart defects have been demonstrated in some patients. A spectrum of behavioral disorders and intellectual disability may also be part of the Aarskog-Scott syndrome phenotype. Female carriers may show some minor manifestations of the disorder, especially in the face and hands.
Mutations in the FGD1 gene (Xp11.21) have been associated with both Aarskog-Scott syndrome and non-syndromic X-linked intellectual disability. One study identified FGD1 mutations in 8 of 46 male patients with a clinical diagnosis of Aarskog-Scott syndrome, including 4 deletions, 1 insertion, and 3 missense mutations. The mutations were scattered over the entire coding sequence, and there were no apparent genotype/phenotype correlations. No global differences in clinical findings were found between probands with or without mutations, but those with mutations presented with a fuller clinical spectrum of the phenotype. Mutations have also been found in a male with attention deficit-hyperactivity disorder (ADHD) and low intelligence quotient with dysmorphic features reminiscent of Aarskog-Scott syndrome, and in three brothers with non-syndromal X-linked mental retardation who lacked distinct craniofacial, skeletal, or genital findings, suggestive of Aarskog-Scott syndrome.
For patients with suspected Aarskog-Scott syndrome, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.
"
