- sSMC - Y-CHROMOSOME

References

 

	Cases without clinical findings	6	Cases with clinical findings	9	symptoms
	similar imbalances - no clinical findings		similar imbalances with clinical findings
			'Turner syndrome' with 46,X,der(Y)
	Cases with unclear clinical correlation		Cases with neocentromeres	2	tumor 0
			similar imbalances
			DISCLAIMER

In general 70% of sSMC carriers are clinically normal. The figures here
are based on the bias, that mainly clinically aberrant cases are reported in literature!

	UPD (uniparental disomy) cases:		UPD Y mat	UPD Y pat	UPD Y unclear

 

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the probably non-dosage sensitive pericentric region of Y-chromosome

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SCHEMATIC CYTOGENETIC DEPICTION

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SCHEMATIC MOLECULARGENETIC DEPICTION

acc. to UCSC Genome Browser on Human Mar. 2006 assembly [UCSC hg18, 2006]
and available BAC-data/ array-data from cases marked *** mentioned below [MB]

 

critical region ? --- ? uncritical region [11.20 centromere 12.50] uncritical region ? --- ? critical region

Below adapted for UCSC hg19, 2009
critical region ? --- ? uncritical region [11.60 centromere 13.40] uncritical region ? --- ? critical region

 

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Clinical symptoms of centromere-near proximal imbalances

 

not done as they should not differ much from XYY-syndrome

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References

Cases without clinical findings (O)

 

	case no.	gender/ age at diagnosis	studied material	de novo/ inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	0Y-O- pter/ 1-1	male/ prenatal	AF	de novo	47,X,i(Y)(qter→q11.221::q11.221→qter),+i(Y)(q11.221)		FISH multiple BAC probes	see below	{21}
		detected prenatally due to elevated blood serum AFP, by normal after birth; at 2 y an undescended testis surgically corrected; normal boy at 11y
	0Y-O- p11.1/ 1-1	female/ 27y	PBL	n.a.	47,XX,+mar[?%]/ 46,XX[?%]	r(Y)(::p11.1→?q11.2::)	FISH, PCR	phenotypically normal woman, ICSI-patient	{11} {23} case Y-1
	0Y-O- p11.1/ 2-1	male/ prenatal	AF	n.a.	47,XY,+mar[100%]	min(Y)(:p11.1→q11.1:)	cenM; subcenM	studied due to AMA	{0} provided by Dr Joksić, Belgrade, Serbia
	0Y-O- q11.1/ 1-2	male/ 41y	PBL	n.a.	47,XY,+inv dup(Y)(q11.?1)[100%]		subcenM	normal male azoospermia	{23} case Y-2

 

O-Cases with similar imbalances NOT caused by sSMC (O-IMB):

 

	case no.	gender/ age at diagnosis	studied material	de novo/ inherited	GTG-banding result and FISH result incl. grade of mosaicism	test methods	clinical symptoms	reference
	0Y-O- IMB- q11/ 1-1	male/ adult	PBL	(paternal)	46,X,der(Y)(pter→p11.23::q12→q11.1::p11.23→qter)	wcp Y	see below	{16}
		normal males (brothers) - abortions in female partner of one

 

	case no.	gender/ age at diagnosis	studied material	de novo/ inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	0Y- CO-1	male/ prenatal	AF	de novo	47,XY,+r[10]/ 46,XY[19]	r(Y)(::p?→q12::)*	SKY; SatIII probe	see below	{3} case 1 {15} case 106 {23} case Y-3
		Amniocentesis due to advanced maternal age; pregnancy continued and normal child born, which develops normal at age of 3y
	0Y- CO-2	see 15-CO-1							{6} {15} case 109
	0Y- CO-3	n.a./ prenatal	AF	de novo	47,+mar[10]/ 46[10]	r(Y)	cen probes wcp Y	see below	{13} case 14
		Amniocentesis due to advanced maternal age; normal child at 2y

 

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References

Cases with clinical findings (W)

 

	case no.	gender/ age at diagnosis	studied material	de novo/ inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	0Y-W- p11.23/ 1-1	male/ 3y	PBL	paternal	47,XX,+r(Y)[100%]	r(Y)(::p11.32→q12::)	different probes	Klinefelter	{10}
	0Y-W- p11.2/ 1-1	male/ 13y	PBL	de novo	47,XY,+mar[32]/ 46,XY[5]	inv dup(Y)(p11.2)	array-CGH	ADHD; hyperactivity	{20} case P-12
	0Y-W- q11.1/ 1-1	male/ 4y	PBL	n.a.	47,X,idic(Y)(q11.1)x2[100%]		n.a.	see below	{17}
		developmental delay, dysmorphic features, hyperactivity, behavioral problems, moderate sensorineural hearing loss, skeletal abnormalities incl. radio-ulnar synostosis
	0Y-W- q11.2/ 1-1	male/ 9y	PBL	de novo	47,X,-Y,+inv dup(Y)x2[60%]/ 46,X,-Y,+inv dup(Y)[40%]	inv dup(Y)(q11.2)	different probes	see below	{8}
		developmental delay, impulsive behavior, prominent alveolar ridges, long philtrum and skeletal abnormalities comprised of radio-ulnar synostosis, asymmetric limb length and fifth finger clinodactyly.
	0Y-W- q11.22~ 11.23/ 1-1	male/ 1 w	PBL	de novo	49,X,+4f(Y)[288]/ 48,X,+3f(Y)[54]/ 47,X,+2f(Y)[10]/ 46,X,+f(Y)[2]/ 45,X	min(Y)(pter→Yq11.22~11.23)*	wcp Y, cep Y, cosY6.65	normal apart from scrotal hypospadias with sinus urogenitalis; rudimentary uterus	{7}

 

W-Cases with similar imbalances NOT caused by sSMC (W-IMB)

none reported yet

 

W-cases with unclear/insufficient characterization of the sSMC (CW):

 

	case no.	gender/ age at diagnosis	studied material	de novo/ inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	0Y- CW-1	male/ 13y	PBL	de novo	47,XY,+?Yq- karyotype was based - apart from banding cytogenetics - mainly on clinical signs	n.a.	n.a.	The boy has psychiatric symptoms typical of boys with the karyotype 47,XYY	{1}
	0Y- CW-2	male/ 22y	PBL	paternal	47,XY,+?Yq- karyotype was based - apart from banding cytogenetics - mainly on clinical signs.	n.a.	n.a.	see below	{2}
		Both had normal intelligence but personality traits look quite similar to those found to be characteristic in males with the karyotype 47,XYY
	0Y- CW-3	male/ postnatal	PBL	n.a.	47,XY,+mar[?%]/ 46,XY[?%]	mar(Y)	DYZ3, cep Y, telYp	bilateral cryptorchidism, hypospadias	{14} case 7
	0Y- CW-3	not clear/ newborn	PBL	father has same Y-chromosome	47,XX,+mar[10]/ 46,XX[40]	r(Y)	cep Y	see below	{18}
		infant was born at term with no complications. Ambiguous genitalia were present with micropenis (1.2 cm stretched penile length), a descended right gonad, no gonad palpable on the left and severe hypospadias. A genitogram showed a large vagina and possible uterine structure with no evidence of a cervix. A scrotal ultrasound study identified the gonad in the right hemi-scrotum as a probable testis. The left gonad could not be identified.--> a descended right ovotestis, an undescended left dysgenetic testis and a uterus lacking endothelial uterine glands. The ovotestis was comprised of approximately 40% testis, 20% dysgenetic testis, 20% ovary, and 20% dysgenetic gonad.

 

 

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References

Cases with unclear clinical correlation (U)

 

	case no.	gender/ age at diagnosis	studied material	de novo/ inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	0Y- U-1	female/ prenatal	AF	de novo	47,XY,+mar[4]/ 46,XY[133]	idic(Y)(q21)	centromeric probe X + Y; locus specific probe SRY	see below	{0} provided by Dr. C. Kelbova, Cottbus, Germany
		chronically colitis ulcerosa with medication in the mother; child born without symptoms; idic turned out to be a cultural artifact
	0Y- U-2	male/ 3.5y	PBL	de novo	47,X,-Y,+marx2[100%]	min(Y)(:p11.31→q11.1:) min(Y)(:p11.2→q11.221:)	MCB	speech and language delay, short stature, mild dysmorphism and Duane anomaly of the eye	{9}
	0Y- U-3	see mult 2-20							{12}
	0Y- U-4	male/ prenatal	PBL	de novo	47,XX,+mar[100%]	inv dup(Y)(p11.2)	array-CGH	studied due to previous child with Down syndrome	{20} case P-13
	0Y- U-5	male/ prenatal	AF	n.a.	47,XY,+mar[100%]	mar(Y)(pter→q11:)	array-CGH	detected prenatally; TOP	{22} case 11
	0Y- U-6	n.a./ prenatal	AF	de novo	47,XX,+mar[100%]	inv dup(Y)(p11.1)	SRY, cep	detected prenatally	{0} provided by Dr. Huhle, Leipzig, Germany
	0Y- U7 to 0Y- U24	male/ postnatal	PBL	n.a.	mos 47,XXY/ 47,XY,+mar	mar(Y)	cepY; cepX	Klinefelter syndrome	{25} 18 cases

 

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References

Cases with neocentromeres (N)

 

	case no.	gender/ age at diagnosis	studied  material	de novo/ inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	0Y-N- pt11.2/ 1-1	male/ prenatal	AF	de novo	47,XX,+mar[100%]	inv dup(Y)(pter→p11.2: :p11.2→pter) aCGH: pter to 10.07 MB	midi, subcenM; aCGH	see below	{19; 24} {20} case P-11 {0}
		Amniocentesis due to advanced maternal age; normal in ultrasound; pregnancy terminated; no abnormalities observed
	0Y-N- qt11.23/ 1-1	female/ 28y	PBL	n.a.	47,XX,+mar[100%]	inv dup(Y)(qter→q11.23: :q11.23→qter)	midi	normal female, infertile	{0} provoded by Dr. Wagner and Stibbe, Hannover, Germany

 

other neocentromere Y cases (no sSMC):

Bukvic N, Susca F, Gentile M, Tangari E, Ianniruberto A, Guanti G.
An unusual dicentric Y chromosome with a functional centromere with no detectable alpha-satellite.
Hum Genet. 1996 Apr;97(4):453-456.

Rivera H, Dominguez MG, Vasquez AI, Ramos AL, Fragoso R.
Centromeric association of a microchromosome in a Turner syndrome patient with a pseudodicentric Y.
Hum Genet. 1993 Nov;92(5):522-524.

Tyler-Smith C, Gimelli G, Giglio S, Floridia G, Pandya A, Terzoli G, Warburton PE, Earnshaw WC, Zuffardi O.
Transmission of a fully functional human neocentromere through three generations.
Am J Hum Genet. 1999 May;64(5):1440-4.

Warburton PE, Cooke CA, Bourassa S, Vafa O, Sullivan BA, Stetten G, Gimelli G, Warburton D, Tyler-Smith C, Sullivan KF, Poirier GG, Earnshaw WC.
Immunolocalization of CENP-A suggests a distinct nucleosome structure at the inner kinetochore plate of active centromeres.
Curr Biol. 1997 Nov 1;7(11):901-904.

Floridia G, Gimelli G, Zuffardi O, Earnshaw WC, Warburton PE, Tyler-Smith C.
A neocentromere in the DAZ region of the human Y chromosome.
Chromosoma. 2000;109(5):318-27.

Conde C, Chheng S, Wu J, Santini M, Kashork CD, Ware S, Scaglia F, Shaffer LG
A novel analphoid marker of the Y chromosome.
Am J Hum Genet 2001; Suppl 69:A765

Assumpcao JG, Berkofsky-Fessler W, Viguetti Campos N, Trevas Maciel-Guerra A, Li S, Melaragno MI, Palandi de Mello M, Warburton PE.
Identification of a neocentromere in a rearranged Y chromosome with no detectable DYZ3 centromeric sequence.
Am J Med Genet. 2002 Dec 1;113(3):263-7.

 

N-Cases with similar imbalances NOT caused by sSMC (N-IMB)

none reported yet