Fabry Disease 2012

Genetic Background

Inheritance

Mode of inheritance for a X linked disease like Fabry

Fabry Disease is inherited in an X-linked manner. Thus there is a 50% change for an affected or a carrier female to pass on Fabry Disease to any of her offspring. Any of her male children will be affected, her female children are obligate carriers and can be affected.

Due to the fact that males only have one X chromosome, they do not pass on the disease to any of their male offspring, but all of their female children are obligate carriers and may even be affected.

(see picture on the right)

Genomic Characteristics

The human X-Chromosome. The location of the GLA gene is highlighted in orange.

The enzyme α-galactosidase is encoded by the gene GLA which is located on the long arm of X chromosome at the locus Xq22.1 (100,652,778 – 100,663,000) (see the figure on the right). It consists of seven exons without any alternate splicing sites and is transcribed on the reverse strand.

The human GLA gene. The green boxes represent the exons. Note the reverse transcription direction.

Reference sequence

Reference Sequence of α-galactosidase A from Uniprot entry P06280

>gi|4504009|ref|NP_000160.1| alpha-galactosidase A precursor [Homo sapiens]
MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFM
EMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNK
TCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWP
FQKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQ
VTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWA
VAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENT
MQMSLKDLL

Mutations

Mutation counts according to HGMD

Mutation type	# of public mutations	# of commerical mutations
Missense/nonsense	354	441
Small deletions	74	97
Small insertions	29	32
Splicing	28	34
Gross deletions	16	27
Small indels	8	10
Complex rearrangements	3	6
Gross insertions/duplications	1	4
Regulatory	1	2
Repeat variations	0	0
Total	514	653